Alpha-hydroperoxyisopropylphenyl compounds and process for preparing the same

ABSTRACT

α-Hydroperoxyisopropylphenyl compounds are useful as an organic hydroxyperoxide content in test compositions for the measurement of peroxide-active substances and are effectively utilized for detecting peroxide-active substances such as blood or hemoglobin (occult blood). 
     Test devices for the detection of occult blood are constituted of a carrier in which organic hydroperoxide, coloration indicator, buffering agent, wetting agent, activating agent and stabilizer are impregnated. If hemoglobin is present in a specimen, the organic hydroperoxide is activated to produce nascent oxygen with which the indicator is oxidized and develops color. Although 2,5-dimethylhexane-2,5-dihydroperoxide and cumene hydroperoxide have been employed as the organic hydroperoxide, they are disadvantageous in remarkable reduction of the detective sensitivity due to lack of the stability with elapse of time, pseudonegative judgement when vitamin C is contained in urine specimen, reduction of capacity in the multi-item test pieces for the detection of urinary components caused by discoloration of the adjacent test pieces, low coloration sensitivity, etc. 
     The compounds of the present invention are improved in the above-mentioned defects. 
     As typical examples of the α-hydroperoxy-isopropylphenyl compounds according to the invention are mentioned 4-(2,4,7-trioxaoctyl) cumene hydroperoxide, 4-(α-operoxyisopropyl)benzyl benzyl ether, 4-octyl cumene -hydroperoxyisopropyl)benzyl benzyl ether, 4-octyl cumene hydroperoxide, bis[4-(α-hydroperoxyisopropyl)benzyl]ether, N,N-dimethyl-]4-(α-hydroperoxyisopropyl)benzene]-sulfoamide and the like.

TECHNICAL FIELD

The present invention relates to α-hydroperoxyisopropylphenyl compoundsand a process for preparing the same.

Furthermore, the invention is concerned with test compositions for themeasurement of peroxide-active substances using as organic hydroperoxidethe above-mentioned α-hydroperoxyisopropylphenyl compounds and testdevices carrying said compositions.

The α-hydroperoxyisopropylphenyl compounds and the compositions or testdevices containing the same are effectively utilized for detectingperoxide-active substances such as blood or hemoglobin.

It may be presumed that if blood or hemoglobin is contained in urine,feces or vomit, certain disease such as inflammation or ulcer progressesin the urinary organs or the digestive system such as the kidneys, thestomach or the intestines. Therefore, in order to promptly diagnose andtreat such disease correct detection of blood or hemoglobin (occultblood) in urine, feces or vomit as mentioned above is important. Theα-hydroperoxyisopropylphenyl compounds of the invention are favorablyused as a reagent for the examination of such occult blood.

BACKGROUND ART

Test devices for the detection of occult blood are constituted of acarrier in which organic hydroperoxide, coloration indicator, bufferingagent, wetting agent, activating agent and stabilizer are impregnated.If hemoglobin is present in a specimen, the organic hydroperoxide isactivated to produce nascent oxygen with which the indicator is oxidizedand develops color. As the organic hydroperoxide are known2,5-dimethylhexane-2,5-dihydroperoxide and cumene hydroperoxide. Whereasthese peroxides are in practical use, they are disadvantageous inremarkably reducing of the detective sensitivity due to lack ofstability with elapse of time, pseudonegative judgement when vitamin Cis contained in the urine specimen, reduction of capacity in themulti-item test pieces for the detection of urinary components caused bydiscoloration of the adjacent test pieces, low coloration sensitivity,etc. Compounds in which the benzene ring of cumene hydroperoxide isprovided with a substituent such as a C₁₋₆ alkyl group, Cl, Br, I, NO₂or carboxyl group have recently been proposed as the hydroperoxide withwhich these disadvantages are improved (Japanese Patent LOP PublicationNo. 190663/1984). Although the peroxides represent considerableimprovement over the known compounds, the stability with elapse of timeis not yet satisfactory.

DISCLOSURE OF THE INVENTION

First, it is an object of the invention to provide peroxides without theabove-mentioned disadvantages and a process for preparing the same.

Second, another object of the invention is to provide test compositionsfor the measurement of peroxide-active substances without theabove-mentioned disadvantages and test devices carrying the same.

These objects are achieved by the present invention as set forth below.

(1) An α-hydroxyperoxyisopropylphenyl compound having the generalformula (I) or (II) ##STR1## wherein R¹, R² and R³ are the same ordifferent and respectively represent hydrogen atom, a lower alkyl group,a halogen atom, carboxyl group, nitro group or a straight- orbranched-chain oxygen-containing alkyl group having one or more etherbonds in the chain or a monovalent organic group containing sulfur atomprovided that at least one of R¹, R² and R³ represents theabove-mentioned straight- or branched-chain oxygen-containing alkylgroup or a monovalent organic group containing sulfur atom; X representsa straight- or branched-chain alkylene group which may contain etherbond and/or phenylene group in the chain or a divalent organic groupcontaining sulfur atom and R⁴ and R⁵ are the same or different andrespectively represent hydrogen atom, a lower alkyl group, a halogenatom, carboxyl group or nitro group.

(2) A compound of the formula (I) according to item 1 wherein theoxygen-containing alkyl group in R¹ -R³ is a group having 2-100 carbonatoms.

(3) A compound of the formula (I) according to item 1 wherein theoxygen-containing alkyl group in R¹ -R³ is an alkyl group represented bythe formula given below. ##STR2## R⁷ -R⁸ being the same or different andrespectively representing hydrogen atom or a lower alkyl group, or##STR3##

(4) A compound of the formula (I) according to item 1 wherein theorganic group in R¹ -R³ is a sulfonyl group represented by the formulagiven below. ##STR4## in which R⁹ represents a straight- orbranched-chain alkyl group, R¹⁰ and R¹¹ are the same or different andrespectively represent a straight- or branched-chain alkyl group or,together with nitrogen atom with which they are bonded, represent afive- or six-membered heterocyclic group which may additionally haveoxygen atom, sulfur atom or nitrogen atom in the ring, Y represents astraight- or branched-chain alkylene group and C represents an integerfrom 0 to 5.

(5) A compound of the general formula (II) according to item 1 whereinthe alkylene group in X is a group having 2-100 carbon atoms.

(6) A compound of the general formula (II) according to item 1 whereinthe alkylene group in X is an alkylene group represented by the formulagiven below. ##STR5##

(7) a compound of the formula (II) according to item 1 wherein theorganic group in X is represented by the formula given below. ##STR6##in which f and g respectively represent an integer from 0 to 5 and eachof R¹² and R¹³ represents a straight- or branched-chain alkyl group.

(8) A process for preparing α-hydroperoxyisopropylphenyl compoundshaving the general formula (I) or (II) according to item 1 whichcomprises oxidizing with an aqueous solution of hydrogen peroxide anα-hydroxyisopropylphenyl compound having the general formula (II) or(IV) ##STR7## wherein R¹ -R⁵ and X respectively have the same meaningsas defined in item 1.

(9) A test composition for the measurement of peroxide-active substancescomprising an α-hydroperoxyisopropylphenyl compound having the generalformula (I) or (II) according to item 1 and an oxidation colorationindicator.

(10) A composition according to item 9 wherein the oxidation colorationindicator is orthotolidine, benzidine or leucomalachite green.

(11) A test device for the measurement of peroxide-active substancescomprising a carrier on which a composition containing anα-hydroperoxyisopropylphenyl compound having the general formula (I) or(II) according to item 1 and an oxidation coloration indicator iscarried.

(12) A test device according to item 11 wherein the carrier is non-wovencloth made of filter paper, glass fibers or a plastic material.

In the above-mentioned formula (I), as described above, R¹, R² and R³are the same or different and respectively represent hydrogen atom, alower alkyl group, a halogen atom, carboxyl group, nitro group or astraight- or branched-chain oxygen-containing alkyl group containing oneor more ether bonds in the chain or a monovalent organic groupcontaining sulfur atom provided that at least one of R¹, R² and R³represents the oxygen-containing alkyl group or the organic group. Theoxygen-containing alkyl group may be either in straight chain or inbranched chain but is required to contain one or more ether bonds in thechain. Number of the carbon atoms in the alkyl group is 2-100,preferably 2-50, although it is not particularly limited. Number of theethers present in the oxygen-containing alkyl group is preferably 1 -7,although there is no limitation to it so far as it is one or more. Saidalkyl group may further be substituted with those substituents whichwill not interfere with coloration of the above-mentioned colorationindicator, for example, halogen atoms (Cl, Br, I), nitro group, hydroxylgroup, sulfone group, carboxyl group, amide group, phenyl group,substituted phenyl group, etc. Preferred examples of such alkyl groupare:

2,4,7-Trioxaoctyl,

2,5,8,11,14,16,19-Heptaoxaeicosanyl,

Methyl-polyethylene glycol-methyl ##STR8## 8-Hydroxy-4-oxaoctyl,1,1-Dimethyl-2,4,7-trioxaoctyl,

2-Oxa-3-phenylpropyl,

(Substituted)phenoxymethyl, and

1,1,3,3-Tetramethylbutyl-polyethylene glycol-methyl ##STR9##

It is desirable that the monovalent organic group

containing sulfur atom contains sulfonyl group ##STR10## As preferredexamples of said group are mentioned groups having the formula givenbelow. ##STR11##

R⁹ in the above-mentioned formula is a straight- or branched-chain alkylgroup containing preferably 1-8 carbon atoms, examples of which includemethyl, ethyl, n-propyl, i-propyl, n-butyl, i-butyl, n-pentyl, n-hexyl,n-heptyl, n-octyl and the like.

R¹⁰ and R¹¹ are the same or different and respectively represent astraight- or branched-chain alkyl group containing preferably 1-4 carbonatoms, examples of which include methyl, ethyl, n-propyl, i-propyl,n-butyl and i-butyl.

Alternatively, R¹⁰ and R¹¹, together with the nitrogen atom with whichthey are bonded, represent a 5- or 6-membered heterocyclic group,examples of which include morpholyl, piperazyl, piperidyl and the like.

Y is an alkylene group containing preferably 1-4 carbon atoms whichinclude, for example, methylene, ethylene, trimethylene, propylene orn-butylene.

c is an integer of preferably 1 or 2.

As especially preferred examples of the monovalent organic groupcontaining sulfur atom are mentioned:

n-Butylsulfonyl ##STR12##

In the above-mentioned formula (II) X represents an alkylene group whichmay optionally contain ether bond and/or phenylene group in the chain orit represents a divalent organic group containing sulfur atom.

The alkylene group may be either in straight chain or in branched chainand contain in the chain one or more, preferably 1-7 ether bonds.Moreover, said alkylene group may contain phenylene group in the chain.In addition, said alkylene group may be substituted with thosesubstituents which will not interfere with color development of thecoloration indicator mentioned above, for example, halogen atoms (Cl,Br, I), nitro group, hydroxyl group, sulfone group, carboxyl group,amide group, phenyl group, substituted phenyl group and the like.

As preferred examples of the above-mentioned alkylene group arementioned:

Trimethylene,

2,2-(3,5,8-Trioxa)nonanylene,

1,7-(4-Hydroxy)heptanylene,

1,3-(2-Oxa)propylene,

1,12-(2,5,8,11-Tetraoxa)decanylene,

1,21-(2,5,8,11,14,17,20-Heptaoxa)heneicosanylene,

Polyethylene glycolyl (mean value for the degree of polymerization 13),

1,14-(2,13-Dioxa)tetradecanylene ##STR13##1,4-Bis[1-(2-oxa-3-propylene)]phenyl,1,13-(7-Hydroxy-4,10-dioxa)tridecanylene,

1,6-(2,5-Dioxa)heptanylene and the like.

As preferred examples of the divalent organic group containing sulfuratom in the chain are mentioned groups having the formula set forthbelow. ##STR14##

In the above formulae f and g are respectively an integer from 0 to 5,preferably from 0 to 2. Each of R¹² and R¹³ is a straight- orbranched-chain alkyl group having preferably 1-4 carbon atoms, methyl,ethyl or n-propyl being particularly preferable.

As especially preferred examples of the above-mentioned divalent organicgroup containing sulfur atom are mentioned: ##STR15##

Methylenesulfonylethylenesulfonylethylenesulfonylmethylene ##STR16##

Sulfonyl-N-methylaminoethoxyethoxyethyl-N-methylaminosulfonyl ##STR17##

Sulfonyl-N-methylaminoethoxyethoxyethoxyethoxy-ethoxyethyl-N-methylaminosulfonyl##STR18##

As typical compounds of the α-hydroperoxyisopropylphenyl compoundsaccording to the invention are mentioned:

4-(2,4,7-Trioxaoctyl)cumene hydroperoxide,

4-(2,5,8,11,14,16,19-Heptaoxaeicosanyl)cumene hydroperoxide,

Polyethylene glycol 4-(α-hydroperoxyisopropyl)-benzylmethyl ether,

4-(8-Hydroxy-4-oxaoctyl)cumene hydroperoxide,

3-(1,1-Dimethyl-2,4,7-trioxaoctyl)cumene hydroperoxide,

4-(α-Hydroperoxyisopropyl)benzyl benzyl ether,

4-(α-Hydroperoxyisopropyl)benzyl 4-nitrobenzyl

4-(α-Hydroperoxyisopropyl)benzyl 3,4,5-trimethoxyphenyl ether,

Polyethylene glycol 4-(α-hydroperoxyisopropyl)benzyl4-(1,1,3,3-tetramethylbutyl)phenyl ether,

3,4-Bis(2,5,8,11,14-pentaoxapentadecanyl)cumene hydroperoxide,

3,4,5-Tris(2-oxa-3-phenylpropyl)cumene hydroperoxide,

1-Chloro-4-(α-hydroperoxyisopropyl)-2-(2-methoxyethoxymethoxymethyl)benzene,

4-(α-Hydroperoxyisopropyl)-2-methylbenzyl benzyl ether,

4-(α-Hydroperoxyisopropyl)-2,6-dichlorobenzyl benzyl ether,

1,3-Bis[4-(α-hydroperoxyisopropyl)phenyl]propane,

2,2-Bis[4-(α-hydroperoxyisopropyl)phenyl]-3,5,8-trioxanonane,

1,7-Bis[4-(α-hydroperoxyisopropyl)phenyl]-4-hydroxyheptane,

4-(α-Hydroperoxyisopropyl)benzyl ether

20 1,12-Bis[4-(α-hydroperoxyisopropyl)phenyl]-2,5,8,11-tetraoxadodecane

1,21-Bis[4-(α-hydroperoxyisopropyl)phenyl]-2,5,8,11,14,17,20-heptaoxaheneicosane,

Polyethylene glycol bis[4-(α-hydroperoxyisopropyl)benzyl]ether,

1,14-Bis[4-(α-hydroperoxyisopropyl)phenyl]-2,13-dioxatetradecane,

1,4-Bis[3-[4-(α-hydroperoxyisopropyl)phenyl]-2-oxapropyl]benzene

1,13-Bis[4-(α-hydroperoxyisopropyl)phenyl]-7-hydroxy-4,10-dioxatridecane,

1,6-Bis[3-(α-hydroperoxyisopropyl)phenyl]-2,5-dioxaheptane,

Bis[2-chloro-4-(α-hydroperoxyisopropyl)benzyl]ether,

1,9-Bis[2-chloro-4-(α-hydroperoxyisopropyl)-phenyl]-2,5,8-trioxanonane,

1,21-Bis[4-(α-hydroperoxyisopropyl)-2-methylphenyl]-2,5,8,11,14,17,20-heptaoxaheneicosane,

1-[4-(α-Hydroperoxyisopropyl)benzenesulfonyl]-butane,

N,N-Dimethyl-[4-(α-hydroperoxyisopropyl)-benzene]sulfoamide,

1-[4-(α-Hydroperoxyisopropyl)benzene]sulfonyl-3,5,8-trioxanonane,

N-[4-(α-Hydroperoxyisopropyl)benzenesulfonyl]-morpholine,

N,N'-Bis[4-(α-hydroperoxyisopropyl)benzenesulfonyl]piperazine,

Bis[4-(α-hydroperoxyisopropyl)benzyl]sulfone,

2-[2-[α-[4-(α-Hydroperoxyisopropyl)toluene]-sulfonyl]ethanesulfonyl]ethanesulfonylmethyl-4-(α-Hydroperoxyisopropyl)benzene,

N,N'-Bis[4-(α-hydroperoxyisopropyl)benzenesulfonyl]-N,N'-dimethyl-3,6,9-trioxaundecane-1,11-diamine,and

N,N'-Bis[4-(α-hydroperoxyisopropyl)-benzenesulfonyl]-N,N'-dimethyl-3,6,9,12,15-pentaoxaheptadecane-1,17-diamine.

The α-hydroperoxyisopropylphenyl compounds represented by theabove-mentioned formula (I) or (II) according to the invention are novelcompounds and are prepared by oxidizing under acid conditions anα-hydroperoxyisopropylphenyl compound represented by the above-mentionedformula (III) or (IV) in an aqueous solution of hydrogen peroxide.Preferably, the α-hydroperoxyisopropylphenyl compound (III) or (IV) isdissolved in an appropriate organic solvent such as ether, and to thesolution are added 30% or 50% aqueous solution of hydrogen peroxide anda small amount of a mineral acid such as sulfuric or hydrochloric acid.The mixture is reacted at room temperature for ten and odd hours. Aftercompletion of the reaction, the desired product is isolated from thereaction product in a conventional manner. For example, water is addedto the reaction mixture, which is then extracted with an appropriateorganic solvent such as ethyl acetate. The solvent is distilled off fromthe extract, and the residue is purified by such means as columnchromatography to obtain the desired product.

The α-hydroperoxyisopropylphenyl compounds (III) or (IV) are produced byreacting a phenyl compound represented by the general formula (V) or(VI) ##STR19## wherein R¹ -R⁵ and X respectively have the same meaningas defined above and Z is a halogen atom with n-butyllithium (ormagnesium) and then with acetone. For example, the two compounds arereacted in an appropriate organic solvent such as, for example,tetrahydrofuran or diethyl ether at -78° C. (in case of n-butyllithium)or a temperature from room temperature to refluxing condition (in caseof magnesium) followed by addition of acetone to produce the compound(III) or (IV).

As described above, the α-hydroperoxyisopropylphenyl compounds (I) or(II) of the invention are used as peroxide in the measurement ofperoxide-active substances, and especially useful for detecting occultblood in urine, feces and vomit.

The test devices comprise a carrier on which a composition constitutedof the α-hydroperoxyisopropylphenyl compound (I) or (II) of theinvention, a coloration indicator, and if needed, buffering agent,wetting agent, activating agent, stabilizer and solvent is impregnated.

As the indicator is used a so-called oxidation indicator develops colorby oxidation. As examples are mentioned orthotolidine, benzidine,leucomalachite green and the like.

The buffering agent is employed for maintaining a constant pH values onthe test device. Preferred agents are, for example, citrate, malonate orsuccinate that can maintain pH value in the range of 4-8 when the testdevice is soaked in a sample. The wetting agent is used in order thatthe sample solution will uniformly be wetted when the test device issoaked in a sample and is preferably exemplified by surface-activeagents such as sodium laurylsulfate, sodium dodecylbenzenesulfonate andsodium dioctylsulfosuccinate. The activating agent is used for enhancingsensitivity of the color-developing reaction on the test device andpreferably is 3-aminoquinoline, quinine, isoquinoline or the like. Asthe stabilizer is used a thickener for preventing elution of the testreagents from the test device, which is preferably a polymer such aspolyvinyl alcohol, polyvinylprrolidone or polyethylene glycol, orgelatin or gum arabic. The solvent may be any of those in which amixture of the above-mentioned reagents is readily soluble, and ethylalcohol, acetone, benzene, toluene, chloroform and the like areadvantageously employed. The carrier may be any one being neithersoluble in nor reactive with the above-mentioned solvent and capable ofabsorbing the above-mentioned composition, a non-woven cloth composed offilter paper, glass fibers or a plastic material being desirable.

Amounts of the α-hydroperoxyisopropylphenyl compound and other reagentsused in the above-mentioned test composition and test device are notcritical but appropriately determined with reference to prior art. As amatter of fact, they are selected so as to be sufficient to causereaction with the subject peroxide-active substance and color-developingreaction.

The invention will be described below in more particular with referenceto examples and test examples.

EXAMPLE 1

4-(2,4,7,-Trioxaoctyl)cumene hydroperoxide ##STR20##

To a solution of 4.56 g (24.4 mmol) of 4-bromobenzyl alcohol in drydichloromethane (48 ml) were added in an atmosphere of argon 3.32 ml(29.1 mmol) β-methoxyethoxymethyl chloride and 6.40 ml (36.7 mmol) ofN,N-diisopropylethylamine, and the mixture was allowed to react at roomtemperature for 15 hours. To the resulting solution was added waterfollowed by extraction with dichloromethane. The organic layer waswashed with water and concentrated under reduced pressure. The residuethus obtained was subjected to silica gel column chromatography forseparation and purification. Elution with dichloromethane yielded 6.18 g(22.5 mmol) of 4-bromo-1-(2,4,7-trioxaoctyl)benzene.

To a solution of 6.18 g (22.5 mmol) of the above-obtained compound indry tetrahydrofuran (180 ml) was added 1.60M hexane solution ofn-butyllithium in the atmosphere of argon at -78° C., and the mixturewas allowed to react for 30 min. To the resulting solution was added 8.3ml (113 mmol) of acetone, and the mixture was reacted at -78° C. for 10min. followed by addition of saturated aqueous solution of ammoniumchloride and extraction with ethyl acetate. The organic layer was washedwith water and subjected to concentration under reduced pressure. Theresidue thus obtained was subjected to silica gel column chromatographyfor separation and purification. Elution with dichloromethane-methanol(25:1) yielded 3.78 g (14.9 mmol) of1-(α-hydroxyisopropyl)-4-(2,4,7-trioxaoctyl)benzene.

To 3.78 g (14.9 mmol) of the above-obtained hydroxy compound were added10 ml of ether, 20 ml of 30% aqueous solution of hydrogen peroxide and0.500 ml of concentrated sulfuric acid, and the mixture was allowed toreact at room temperature for 18 hours followed by addition of water andextraction with ethyl acetate. The organic layer was washed with waterand concentrated under reduced pressure. The residue thus obtained wassubjected to silica gel column chromatography for separation andpurification. Elution with ethyl acetate-hexane (1:1) yielded 3.30 g(12.2 mmol) of 4-(2,4,7-trioxaoctyl)cumene hydroperoxide.

NMR (ppm, CDCl₃)

8.22(s, 1 H), 7.48-7.17(m, 4 H), 4.73(s, 2 H),

4.57(s, 2 H), 3.82-3.43(m, 4 H), 3.35(s, 3 H),

1.57(s, 6 H).

IR(νcm⁻¹,CHCl₃) 3530, 3330.

EXAMPLE 2

4-(2,5,8,11,14,16,19-Heptaoxaeicosanyl)cumene hydroperoxide ##STR21##

To a solution of 1.49 g (37.3 mmol) of sodium hydride contained at 60%in mineral oil in dry dimethylformamide (70 ml) was added 7.00 g (24.8mmol) of 3,6,9,12,14,17-hexaoxaoctadeca-1-nol in an atmosphere of argon,and the mixture was allowed to react at 40°-50° C. for 30 min. To thereaction mixture was added 5.17 g (20.7 mmol) of 4-bromobenzyl bromideat room temperature for 16 hours. To the reaction mixture at 0° C. wasadded a saturated aqueous solution of ammonium chloride followed byextraction with ethyl acetate. The organic layer was washed with waterand concentrated under reduced pressure. The residue thus obtained wassubjected to silica gel column chromatography for separation andpurification. Elution with dichloromethane yielded 8.03 g (17.8 mmol) of1-bromo-4-(2,5,8,11,14,16,19-heptaoxaeicosanyl)benzene.

To a solution of 8.03 g (17.8 mmol) of the above-obtained compound indry tetrahydrofuran (200 ml) was added 1.60M hexane solution ofn-butyllithium (16.7 ml, 26.7 mmol) in the atmosphere of argon at -78°C. The mixture was allowed to react for 30 min. To the solution wasadded 6.50 ml (88.5 mmol) of acetone, and the mixture was reacted at-78° C. for 10 min. To the reaction mixture was added a saturatedaqueous solution of ammonium chloride followed by extraction with ethylacetate. The organic layer was washed with water and concentrated underreduced pressure. The residue thus obtained was subjected to silica gelcolumn chromatography for separation and purification. Elution withdichloromethane-methanol(50:1) yielded 7.28 g (16.9 mmol) of4-(2,5,8,11,14,16,19-heptaoxaeicosanyl)-1-(α-hydroxyisopropyl)benzene.

To 7.28 g (16.9 mmol) of the above-obtained hydroxy compound were added20 ml of ether, 40 ml of 30% aqueous solution of hydrogen peroxide and1.00 ml of concentrated sulfuric acid. The mixture was allowed to reactat room temperature for 15 hours followed by addition of water andextraction with ethyl acetate. The organic layer was washed with waterand concentrated under reduced pressure. The residue thus obtained wassubjected to silica gel column chromatography for separation andpurification. Elution with ethyl acetate-hexane (2:1) yielded 5.36 g(12.0 mmol) of 4-(2,5,8,11,14,16,19-heptaoxaeicosanyl)cumenehydroperoxide.

NMR (ppm, CDCl₃)

8.48(s, 1 H), 8.47-8.17(m, 4 H), 4.68(s, 2 H),

4.50(s, 2 H), 3.63 (s, 2 H), 3.35(s, 3 H), 1.57(s, 6 H) .

IR(νcm⁻¹,CHCl₃) 3530, 3330.

EXAMPLE 3

Polyethylene glycol 4-(α-hydroperoxyisopropyl)benzyl methyl ether##STR22##

To a solution of 1.63 g (40.8 mmol) of sodium hydride contained at 60%in mineral oil in dry dimethylformamide (60 ml) was added in anatmosphere of argon 4.94 g (6.59 mmol on average) of polyethylene glycolmethyl ether with an average molecular weight of 750, and the mixturewas allowed to react at 40°-50° C. for 30 min. To the reaction mixturewas added 2.47 g (9.88 mmol) of 4-bromobenzyl bromide, and the mixturewas allowed to react at room temperature for 16 hours. To the reactionmixture at 0° C. was added a saturated aqueous solution of ammoniumchloride followed by extraction with ethyl acetate. The organic layerwas washed with water and concentrated under reduced pressure. Theresidue thus obtained was subjected to silica gel column chromatographyfor separation and purification.

Elution with dichloromethane-methanol (50:1) yielded 3.81 g (4.15 mmolon average) of a compound of the structure shown below. ##STR23##

To a solution of 3.81 g (4.15 mmol on average) of the above-obtainedcompound in dry tetrahydrofuran (40 ml) was added 1.60M hexane solutionof n-butyllithium (3.90 ml, 6.24 mmol) in the atmosphere of argon at-78° C., and the mixture was allowed to react for 30 min. To thesolution was added 2.60 ml (35.4 mmol) of acetone, and the mixture wasallowed to react at -78° C. for 10 min. To the reaction mixture wasadded a saturated aqueous solution of ammonium chloride followed byextraction with ethyl acetate. The organic layer was washed with waterand concentrated under reduced pressure. The residue thus obtained wassubjected to silica gel column chromatography for separation andpurification. Elution with dichloromethane-methanol (50:1) yielded 2.19g (2.48 mmol on average) of a compound of the structure shown below.##STR24##

To 2.19 g (2.48 mmol on average) of the above-obtained hydroxy compoundwere added 20 ml of ether, 40 ml of a 30% aqueous solution of hydrogenperoxide and 1.00 ml of concentrated sulfuric acid. The mixture wasallowed to react at room temperature for 18 hours followed by additionof water and extraction with ethyl acetate. The organic layer was washedwith water and concentrated under reduced pressure. The residue thusobtained was subjected to silica gel column chromatography forseparation and purification. Elution with dichloromethane-methanol(25:1) yielded 1.06 g (1.18 mmol on average) of the desired product.

NMR (ppm, CDCl₃)

8.30(bs, 1 H), 7.47-7.10(m, 4 H), 4.50(s, 2 H),

3.63(s, 64 H), 3.33(s, 3 H), 1.48(s, 6 H).

IR(νcm⁻¹,CHCl₃) 3530, 3330.

EXAMPLE 4

4-(8-Hydroxy-4-oxaoctyl)cumene hydroperoxide ##STR25##

To a solution of 1.00 g (10.2 mmol) of 1,4-butanediol in 20 ml of drydimethylformamide were added 2.80 g (10.2 mmol) oftert-butyldiphenylsilyl chloride and 3.47 g (51.0 mmol) of imidazole inan atmosphere of argon. The mixture was allowed to react at 0° C. for 24hours. To the solution was added water followed by extraction withdichloromethane. The organic layer was washed with water andconcentrated under reduced pressure. The residue thus obtained wassubjected to silica gel column chromatography for separation andpurification. Elution with dichloromethane-methanol (100:1) yielded 2.17g (6.62 mmol) of 4-(tert-butyldiphenylsiloxy)-1-butanol.

To a solution of 2.17 g (6.62 mmol) of said compound in dry pyridine (48ml) was added 1.39 g (7.29 mmol) of p-toluenesulfonyl chloride in theatmosphere of argon. The mixture was allowed to react at roomtemperature for 6 hours followed by addition of water and extractionwith benzene. The organic layer was washed with water and concentratedunder reduced pressure. The residue thus obtained was subjected tosilica gel column chromatography for separation and purification.Elution with dichloromethane-hexane (1:2) yielded 2.94 g (6.10 mmol) of4-(tert-butyldiphenylsiloxy)-1-(p-toluenesulfoxy)butane.

Next, to a solution of 405 mg (10.1 mmol) of sodium hydride contained at60% in mineral oil in dry dimethylformamide (20 ml) was added 1.44 g(6.70 mmol) of 3-(4-bromophenyl)-1-propanol in the atmosphere of argon,and the mixture was allowed to react at 100° C. for 30 min. To thereaction mixture was then added 2.94 g (6.10 mmol) of4-(tert-butyldiphenylsiloxy)-1-(p-toluenesulfoxy)butane, and the mixturewas reacted at 100° C. for 16 hours. To the reaction mixture at 0° C.was added a saturated aqueous solution of ammonium chloride followed byextraction with benzene. The organic layer was washed with water andthen concentrated under reduced pressure. The residue thus obtained wassubjected to silica gel column chromatography for separation andpurification. Elution with dichloromethane-hexane (1:4) yielded 1.29 g(2.46 mmol) of4-[8-(tert-butyldiphenylsiloxy)-4-oxaoctyl]-1-bromobenzene.

To a solution of 1.29 g (2.46 mmol) of the above-obtained compound indry tetrahydrofuran (50 ml) was added 1.60M hexane solution ofn-butyllithium (1.85 ml, 2.96 mmol) in the atmosphere of argon at -78°C., and the mixture was allowed to react for 30 min. To the solution wasadded 1.00 ml (13.6 mmol) of acetone, and the mixture was reacted at-78° C. for 10 min. followed by addition of saturated solution ofammonium chloride and extraction with ethyl acetate. The organic layerwas washed with water and then concentrated under reduced pressure. Theresidue thus obtained was subjected to silica gel column chromatographyfor separation and purification. Elution with dichloromethane-methanol(100:1) yielded 898 mg (1.84 mmol) of4-[8-(tert-butyldiphenylsiloxy)-4-oxaoctyl]-1-(α-hydroxyisopropyl)-benzene.

To 898 mg (1.84 mmol) of the above-obtained hydroxy compound were added5 ml of ether, 10 ml of a 30% aqueous solution of hydrogen peroxide and0.25 ml of concentrated sulfuric acid. The mixture was allowed to reactat room temperature for 11 hours followed by addition of water andextraction with ethyl acetate. The organic layer was washed with waterand then concentrated under reduced pressure. The residue thus obtainedwas subjected to silica gel column chromatography for separation andpurification. Elution with ethyl acetate-hexane (1:2) yielded 853 mg(1.69 mmol) of 4-[8-(tert-butyldiphenylsiloxy)-4-oxaoctyl]cumenehydroperoxide.

Next, to a solution of 853 mg (1.69 mmol) of the above-obtained compoundin dry tetrahydrofuran (16 ml) was added a 1.0M tetrahydrofuran solutionof tetrabutylammonium fluoride (3.40 ml, 3.40 mmol) in the atmosphere ofargon, and the mixture was allowed to react at room temperature for 6hours. To the solution was added water, and the mixture was extractedwith ethyl acetate. The organic layer was washed with water and thenconcentrated under reduced pressure. The residue thus obtained wassubjected to silica gel column chromatography for separation andpurification. Elution with dichloromethane-methanol yielded 428 mg (1.52mmol) of 4-(8-hydroxy-4-oxaoctyl)cumene hydroperoxide.

NMR (ppm, CDCl₃)

8 03(s, 1 H), 7.38-7.04(m, 4 H), 3.52-3.16

(m, 6 H), 2.56-2.23(m, 2 H), 2.06-1.77(m, 6 H),

1.56(s, 6 H).

IR(νcm⁻¹,CHCl₃) 3610, 3530, 3400.

EXAMPLE 5

3-(1,1-Dimethyl-2,4,7-trioxaoctyl)cumene hydroperoxide ##STR26##

To a solution of 3.34 g (16.8 mmol) of 3'-bromoacetophenone in drydiethyl ether (68 ml) was added 1.4M diethyl ether solution ofmethyllithium (18.0 ml, 25.2 mmol) in an atmosphere of argon at 0° C.,and the mixture was allowed to react for 30 min. To the solution wasadded a saturated aqueous solution of ammonium chloride, and the mixturewas extracted with ethyl acetate. The organic layer was washed withwater and then concentrated under reduced pressure. The residue thusobtained was subjected to silica gel column chromatography forseparation and purification. Elution with dichloromethane-methanolyielded 3.47 g (16.1 mmol) of 3-(α-hydroxyisopropyl)-1-bromobenzene.

To a solution of 3.47 g (16.1 mmol) of the above-obtained compound indry dichloromethane (35 ml) were added in the atmosphere of argon 2.20ml (19.3 mmol) β-methoxyethoxy methyl chloride and 4.20 ml (24.1 mmol)of N,N-diisopropylethylamine, and the mixture was refluxed for 16 hours.To the solution was added water, and the mixture was extracted withdichloromethane. The organic layer was washed with water andconcentrated under reduced pressure. The residue thus obtained wassubjected to silica gel column chromatography for separation andpurification. Elution with dichloromethane yielded 4.34 g (14.3 mmol) of3-(1,1-dimethyl-2,4,7-trioxaoctyl)-1-bromobenzene.

To a solution of 4.34 g (14.3 mmol) of the above-obtained compound indry tetrahydrofuran (160 ml) was added 1.60M hexane solution ofn-butyllithium (13.4 ml, 21.4 mmol) in the atmosphere of argon at -78°C., and the mixture was allowed to react for 30 min. To the solution wasadded 5.30 ml (72.2 mmol) of acetone, and the mixture was reacted -78°C. for 10 min. followed by addition of a saturated aqueous solution ofammonium chloride and extraction with ethyl acetate. The organic layerwas washed with water and then concentrated under reduced pressure. Theresidue thus obtained was subjected to silica gel column chromatographyfor separation and purification. Elution with dichloromethane-methanol(50:1) yielded 3.51 g (12.4 mmol) of3-(1,1-dimethyl-2,4,7-trioxaoctyl)-1-(α-hydroxyisopropyl)-benzene.

To 3.51 g (12.4 mmol) of the above-obtained hydroxy compound were added20 ml of ether, 40 ml of a 30% aqueous solution of hydrogen peroxide and1.00 ml of concentrated sulfuric acid, and the mixture was allowed toreact at room temperature for 14 hours followed by addition of water andextraction with ethyl acetate. The organic layer was washed with waterand then concentrated under reduced pressure. The residue thus obtainedwas subjected to silica gel column chromatography for separation andpurification. Elution with ethyl acetate-hexane (1:1) yielded 3.07 g(10.3 mmol) of 3-(1,1-dimethyl-2,4,7-trioxaoctyl)cumene hydroperoxide.

NMR (ppm, CDCl₃)

8.20(s, 1 H), 7.55-7.23(m, 4 H), 4.71(s, 2 H),

3.85-3.31(m, 4 H), 3.33(s, 3 H), 1.95(s, 6 H),

1.55(s, 6 H).

IR(νcm⁻¹,CHCl₃) 3530, 3320.

EXAMPLE 6

4-(α-Hydroperoxyisopropyl)benzyl benzyl ether ##STR27##

To a solution of 1.07 g (26.8 mmol) of sodium hydride contained at 60%in mineral oil in dry dimethylformamide (80 ml) was added 4.02 g (21.5mmol) of benzyl alcohol in an atmosphere of argon, and the mixture wasallowed to react at 40°-50° C. for 30 min. To the reaction mixture wasthen added 4.47 g (17.9 mmol) of 4-bromobenzyl bromide, and the mixturewas allowed to react at room temperature for 19 hours. To the reactionmixture at 0° C. was added a saturated aqueous solution of ammoniumchloride, and the mixture was extracted with ethyl acetate. The organiclayer was washed with water and then concentrated under reducedpressure. The residue thus obtained was subjected to silica gel columnchromatography for separation and purification. Elution withdichloromethane-hexane (1:2) yielded 4.61 g (16.6 mmol) of 4-bromophenylbenzyl ether.

To a solution of 4.61 g (16.6 mmol) of the above-obtained compound indry tetrahydrofuran (100 ml) was added 1.21 g (49.8 mmol) of magnesiumin the atmosphere of argon, and the mixture was allowed to react at roomtemperature for 2 hours. To the solution was added 7.50 ml (102 mmol) ofacetone, and the mixture was reacted at 0° C. for 10 min. followed byaddition of a saturated aqueous solution of ammonium chloride andextraction with ethyl acetate. The organic layer was washed with waterand then concentrated under reduced pressure. The residue thus obtainedwas subjected to silica gel column chromatography for separation andpurification. Elution with dichloromethane-methanol (100:1) yielded 3.45g (13.5 mmol) of 4-(α-hydroxyisopropyl)-benzyl benzyl ether.

To 3.45 g (13.5 mmol) of the above-obtained hydroxy compound were added10 ml of ether, 20 ml of a 30% aqueous solution of hydrogen peroxide and0.50 ml of concentrated sulfuric acid. The mixture was allowed to reactat room temperature for 14 hours followed by addition of water andextraction with ethyl acetate. The organic layer was washed with waterand then concentrated under reduced pressure. The residue thus obtainedwas subjected to silica gel column chromatography for separation andpurification. Elution with ethyl acetate-hexane (1:2) yielded 3.23 g(11.9 mmol) of 4-(α-hydroperoxyisopropyl)benzyl benzyl ether.

NMR (ppm, CDCl₃)

8.23(bs, 1 H), 7.52-7.20(m, 9 H), 4.52(s, 4 H),

5 1.57(s, 6 H).

IR(νcm⁻¹,CHCl₃) 3530, 3320.

EXAMPLE 7

4-(α-Hydroperoxyisopropyl)benzyl 4-nitrobenzyl ether ##STR28##

To a solution of 812 mg (20.3 mmol) of sodium hydride contained at 60%in mineral oil in dry dimethylformamide (100 ml) was added 3.01 g (16.1mmol) of 4-bromobenzyl alcohol in the atmosphere of argon, and themixture was allowed to react at 40°-50° C. for 30 min. followed byaddition of 2.85 g (13.2 mmol) of 4-nitrobenzyl bromide. The mixture wasreacted at room temperature for 17 hours. To the reaction mixture at 0°C. was added saturated aqueous solution of ammonium chloride followed byextraction with ethyl acetate. The organic layer was washed with waterand then concentrated under reduced pressure. The residue thus obtainedwas subjected to silica gel column chromatography for separation andpurification. Elution with dichloromethane-hexane (1:1) yielded 2.76 g(8.57 mmol) of 4-bromobenzyl 4-nitrobenzyl ether.

To a solution of 2.76 g (8.57 mmol) of the above-mentioned compound indry tetrahydrofuran (90 ml) at -78° C. was added 1.60M hexane solutionof n-butyllithium (6.43 ml, 10.3 mmol), and the mixture was allowed toreact for 30 min. To the resulting solution was added 3.20 ml (43.6mmol) of acetone, and the mixture was allowed to react at -78° C. for 10min. To the reaction mixture was added a saturated aqueous solution ofammonium chloride followed by extraction with ethyl acetate. The organiclayer was washed with water and then concentrated under reducedpressure. The residue thus obtained was subjected to silica gel columnchromatography for separation and purification. Elution withdichloromethane-methanol (50:1) yielded 1.37 g (4.55 mmol) of4-(α-hydroxyisopropyl)benzyl 4-nitrobenzyl ether.

To 1.37 g (4.55 mmol) of the above-obtained hydroxy compound were added10 ml of ether, 20 ml of a 30% aqueous solution of hydrogen peroxide and0.50 ml of concentrated sulfuric acid. The mixture was allowed to reactat room temperature for 16 hours followed by addition of water andextraction with ethyl acetate. The organic layer was washed with waterand then concentrated under reduced pressure. The residue thus obtainedwas subjected to silica gel column chromatography for separation andpurification. Elution with ethyl acetate-hexane (1:1) yielded 1.01 g(3.19 mmol) of 4-(α-Hydroperoxyisopropyl)benzyl 4-nitrobenzyl ether.

NMR (ppm, CDCl₃)

8.23(s, 1 H), 8.06(d, 2 H, J=7 Hz), 7.55-7.23(m, 6 H), 4,78(s, 2 H),4.55(s, 2 H), 1.53(s, 6 H).

IR(νcm⁻¹, CHCl₃) 3530, 3330.

EXAMPLE 8

4-(α-Hydroperoxyisopropyl)benzyl 3,4,5-trimethoxyphenyl ether ##STR29##

To a solution of 1.46 g (36.5 mmol) of sodium hydride contained at 60%in mineral oil in dry dimethylformamide (50 ml) was added 2.02 g (11.0mmol) of 3,4,5-trimethoxyphenol in an atmosphere of argon, and themixture was allowed to react at 0° C. for 15 min. To the reactionmixture was added 3.60 g (14.4 mmol) of 4-bromobenzyl bromide. Theresulting mixture was reacted at room temperature for 24 hours. To thereaction mixture at 0° C. was added a saturated aqueous solution ofammonium chloride followed by extraction with ethyl acetate. The organiclayer was washed with water and then concentrated under reducedpressure. The residue thus obtained was subjected to silica gel columnchromatography for separation and purification. Elution withdichloromethane-hexane (1:1) yielded 3.28 g (9.28 mmol) of 4-bromobenzyl3,4,5-trimethoxyphenyl ether.

To a solution of 3.28 g (9.28 mmol) of the above-obtained compound indry tetrahydrofuran (120 ml) at -78° C. was added 1.60M hexane solutionof n-butyllithium (8.70 ml, 13.9 mmol) in the atmosphere of argon, andthe mixture was allowed to react for 30 min. To the solution was added3.40 ml (46.3 mmol) of acetone, and the mixture was reacted at -78° C.for 10 min. To the reaction mixture was added a saturated aqueoussolution of ammonium chloride followed by extraction with ethyl acetate.The organic layer was washed with water and then concentrated underreduced pressure. The residue thus obtained was subjected to silica gelcolumn chromatography for separation and purification. Elution withethyl acetate-hexane (1:3) yielded 1.72 g (5.17 mmol) of4-(α-hydroxyisopropyl)benzyl 3,4,5-trimethoxyphenylether.

To 1.72 g (5.17 mmol) of the above-obtained hydroxy compound were added10 ml of ether, 20 ml of a 30% aqueous solution of hydrogen peroxide and0.500 ml of concentrated sulfuric acid. The mixture was allowed to reactat room temperature for 15 hours followed by addition of water andextraction with ethyl acetate. The organic layer was washed with waterand then concentrated under reduced pressure. The residue thus obtainedwas subjected to silica gel column chromatography for separation andpurification. Elution with ethyl acetate-hexane (1:1) yielded 1.48 g(4.25 mmol) of 4-(α-hydroxyisopropyl)benzyl 3,4,5-trimethoxyphenylether.

NMR (ppm, CDCl₃)

8.67(bs, 1 H), 7.53-7.27(m, 4 H), 4.95(s, 2 H),

3.77(s, 9 H), 1.57(s, 3 H).

IR(νcm⁻¹,CHCl₃) 3530, 3330.

EXAMPLE 9

Polyethylene glycol 4-(α-hydroperoxyisopropyl)benzyl4-(1,3-dimethylbutyl)phenyl ether ##STR30##

To a solution of 2.14 g (53.4 mmol) of sodium hydride contained at 60%in mineral oil in dry dimethylformamide (120 ml) was added 5.66 g (8.76mmol on average) of Triton X-100 in an atmosphere of argon, and themixture was allowed to react at 40°-50° C. for 30 min. To the reactionmixture was added 4.41 g (17.6 mmol) of 4-bromobenzyl bromide, and themixture was reacted at 60° C. for 30 min. To the reaction mixture at 0°C. was added a saturated aqueous solution of ammonium chloride followedby extraction with ethyl acetate. The organic layer was washed withwater and then concentrated under reduced pressure. The residue thusobtained was subjected to silica gel column chromatography forseparation and purification. Elution with dichloromethane-hexane (4:1)yielded 2.54 g (3.12 mmol on average) of a compound of the structureshown below. ##STR31##

To a solution of 2.54 g (312 mmol on average) of the above-obtainedcompound in dry tetrahydrofuran (80 ml) at -78° C. was added 1.60Mhexane solution of n-butyllithium (4.00 ml, 6.40 mmol) in the atmosphereof argon, and the mixture was allowed to react for 30 min. To thesolution was added 5.00 ml (68.1 mmol) of acetone, and the mixture wasallowed to react at -78° C. for 10 min. To the reaction mixture wasadded a saturated aqueous solution of ammonium chloride followed byextraction with ethyl acetate. The organic layer was washed with waterand then concentrated under reduced pressure. The residue thus obtainedwas subjected to silica gel column chromatography for separation andpurification. Elution with dichloromethane-methanol (25:1) yielded 2.89g (3.64 mmol on average) of a compound of the structure shown below.##STR32##

To 2.89 g (3.64 mmol on average) of said hydroxy compound were added 10ml of ether, 20 ml of a 30% aqueous solution of hydrogen peroxide and0.500 ml of concentrated sulfuric acid, and the mixture was allowed toreact at room temperature for 48 hours followed by addition of water andextraction with ethyl acetate. The organic layer was washed with waterand then concentrated under reduced pressure. The residue thus obtainedwas subjected to silica gel column chromatography for separation andpurification. Elution with dichloromethane-methanol (25:1) yielded 1.40g (1.73 mmol on average) of the desired product.

NMR (ppm, CDCl₃)

9.07(bs, 1 H), 7.62-6.83(m, 8 H), 4.60(s, 4 H),

3.73(s, 40 H), 1.82(s, 2 H), 1.67(s, 6 H),

1.46(s, 6 H), 0.83(s, 9 H).

IR(νcm⁻¹,CHCl₃) 3520.

EXAMPLE 10

3,4-Bis(2,5,8,11,14-pentaoxapentadecanyl)cumene hydroperoxide ##STR33##

To a solution of 4.13 g (22.3 mmol) of 3,4-dimethyl-1-bromobenzene incarbon tetrachloride (160 ml) were added 8.73 g (49.0 mmol) ofN-bromosuccinimide and 150 mg (0.62 mmol) of benzoyl peroxide in anatmosphere of argon, and the mixture was refluxed for 18 hours. To thereaction mixture was added water followed by extraction with benzene.The organic layer was washed with water and concentrated under reducedpressure. The residue thus obtained was subjected to silica gel columnchromatography for separation and purification. Elution withhexane-dichloromethane (10:1) yielded 2.57 g (7.49 mmol) of3,4-bis(bromomethyl)-1-bromobenzene.

Next, 3.74 g (18.0 mmol) of 3,6,9,12-tetraoxa-1-tridecanol was added toa solution of 1.92 g (48.0 mmol) of sodium hydride contained at 60% inmineral oil in dry dimethylformamide (65 ml) in the atmosphere of argon,and the mixture was allowed to react at 40°-50° C. for 30 min. Then, tothe reaction mixture was added 2.57 g (7.49 mmol) of3,4-bis(bromomethyl)-1-bromobenzene, and the mixture was reacted at roomtemperature for 19 hours. To the reaction mixture at 0° C. was added asaturated aqueous solution of ammonium chloride followed by extractionwith ethyl acetate. The organic layer was washed with water and thenconcentrated under reduced pressure. The residue thus obtained wassubjected to silica gel column chromatography for separation andpurification. Elution with dichloromethane yielded 3.08 g (5.16 mmol) of3,4-bis(2,5,8,11,14-pentaoxapentadecanyl)-1-bromobenzene.

To a solution of 3.08 g (5.16 mmol) of the above-obtained compound indry tetrahydrofuran (150 ml) at -78° C. was added 1.60M hexane solutionof n-butyllithium (4.80 ml, 7.68 mmol) in the atmosphere of argon, andthe mixture was allowed to react for 30 min. To the solution was added1.90 ml (25.9 mmol) of acetone, and the mixture was reacted at -78° C.for 10 min. To the reaction mixture was added a saturated aqueoussolution of ammonium chloride followed by extraction with ethyl acetate.The organic layer was washed with water and then concentrated underreduced pressure. The residue thus obtained was subjected to silica gelcolumn chromatography for separation and purification. Elution withdichloromethane-methanol (50:1) yielded 2.56 g (4.44 mmol) of3,4-bis(2,5,8,11,14-pentaoxapentadecanyl)-1-(α-hydroxyisopropyl)benzene.

To 2.56 g (4.44 mmol) of the above-obtained hydroxy compound were added10 ml of ether, 20 ml of a 30% aqueous solution of hydrogen peroxide and0.50 ml of concentrated sulfuric acid, and the mixture was allowed toreact at room temperature for 15 hours followed by addition of water andextraction with ethyl acetate. The organic layer was washed with waterand then concentrated under reduced pressure. The residue thus obtainedwas subjected to silica gel column chromatography for separation andpurification. Elution with ethyl acetate-hexane (2:1) yielded 2.26 g(3.82 mmol) of 3,4-bis(2,5,8,11,14-pentaoxapentadecanyl)cumenehydroperoxide.

NMR (ppm, CDCl₃)

8 12(s, 1 H), 7.53-7.21(m, 3 H), 4.56(s, 4 H),

3.68(s, 32 H), 3.35(s, 6 H), 1.51(s, 6 H).

IR(νcm⁻¹,CHCl₃) 3530, 3320.

EXAMPLE 11

3,4,5-Tris(2-oxa-3-phenylpropyl)cumene hydroperoxide ##STR34##

To a solution of 3.63 g (18.2 mmol) of 3,4,5-trimethyl-1-bromobenzene incarbon tetrachloride (200 ml) were added 10.7 g (60.1 mmol) ofN-bromosuccinimide and 165 mg (0.68 mmol) of benzoyl peroxide in anatmosphere of argon, and the mixture was refluxed for 24 hours. To thereaction mixture was added water followed by extraction with benzene.The organic layer was washed with water and concentrated under reducedpressure. The residue thus obtained was subjected to silica gel columnchromatography for separation and purification. Elution withhexane-dichloromethane (10:1) yielded 1.51 g (3.46 mmol) of3,4,5-tris(bromomethyl)-1bromobenzene.

To a solution of 726 mg (18.2 mmol) of sodium hydride contained at 60%in mineral oil in dry dimethylformamide (30 ml) was added 1.31 g (12.1mmol) of benzyl alcohol in the atmosphere of argon, and the mixture wasallowed to react at 40 -50° C. for 30 min. To the reaction mixture wasadded 1.51 g (3.46 mmol) of 3,4,5-tris(bromomethyl)-1-bromobenzene, andthe mixture was reacted at room temperature for 40 hours. To thereaction mixture at 0° C. was added a saturated aqueous solution ofammonium chloride followed by extraction with ethyl acetate. The organiclayer was washed with water and then concentrated under reducedpressure. The residue thus obtained was subjected to silica gel columnchromatography for separation and purification. Elution withdichloromethane (1:1) yielded 1.04 g (2.01 mmol) of 3,4,5-tris(2-oxa-3-phenylpropyl)-1-bromobenzene.

To a solution of 1.04 g (2.01 mmol) of the above-obtained compound indry tetrahydrofuran (20 ml) at -78° C. was added 1.60M hexane solutionof n-butyllithium (1.90 ml, 3.04 mmol) in the atmosphere of argon, andthe mixture was allowed to react for 30 min. To the solution was added1.50 ml (20.4 mmol) of acetone, and the mixture was reacted at -78° C.for 10 min. To the reaction mixture was added a saturated aqueoussolution of ammonium chloride followed by extraction with ethyl acetate.The organic layer was washed with water and then concentrated underreduced pressure. The residue thus obtained was subjected to silica gelcolumn chromatography for separation and purification. Elution withdichloromethane-methanol (100:1) yielded 917 mg (1.85 mmol) of3,4,5-tris(2-oxa-3-phenylpropyl)-1-(α-hydroxyisopropyl)benzene.

To 917 mg (1.85 mmol) of the above-obtained hydroxy compound were added5 ml of ether, 10 ml of a 30% aqueous solution of hydrogen peroxide and0.25 ml of concentrated sulfuric acid, and the mixture was allowed toreact at room temperature for 16 hours followed by addition of water andextraction with ethyl acetate. The organic layer was washed with waterand then concentrated under reduced pressure. The residue thus obtainedwas subjected to silica gel column chromatography for separation andpurification. Elution with ethyl acetate-hexane (1:2) yielded 831 mg(1.62 mmol) of 3,4,5-tris(2-oxa-3-phenyl-propyl)cumene hydroperoxide.

NMR (ppm, CDCl₃)

8.30(s, 1 H), 7.38(s, 2 H), 7.30(s, 15 H),

4.55(s, 12 H), 1.53(s, 6 H)

IR(νcm⁻¹,CHCl₃) 3530, 3330.

EXAMPLE 12

1-Chloro-4-(α-hydroperoxyisopropyl)-2-(2-methoxyethoxymethoxymethyl)benzene##STR35##

To a solution of 100 g (4.52 mmol) of 5-bromo-2-chlorobenzyl alcohol indry dichloromethane (20 ml) were added 675 mg (5.42 mmol) of2-methoxyethoxymethyl chloride and 1.20 ml (6.89 mmol) ofN,N-diisopropylethylamine in an atmosphere of argon, and the mixture wasallowed to react at room temperature for 18 hours. To the reactionsolution at 0° C. was a added saturated aqueous solution of ammoniumchloride followed by extraction with ethyl acetate. The organic layerwas washed with water and then concentrated under reduced pressure. Theresidue thus obtained was subjected to silica gel column chromatographyfor separation and purification. Elution with dichloromethane-hexane(1:5) yielded 1.23 g (3.98 mmol) of4-bromo-1-chloro-2-(2-methoxyethoxymethoxymethyl)benzene.

To a solution of 1.23 g (3.98 mmol) of the above-obtained compound indry tetrahydrofuran (30 ml) at -78° C. was added 1.60M hexane solutionof n-butyllithium (2.99 ml, 4.78 mmol) in the atmosphere of argon, andthe mixture was allowed to react for 30 min. To the solution was added5.0 ml (68.0 mmol) of acetone, and the mixture was reacted at -78° C.for 10 min. followed by addition of saturated aqueous solution ofammonium chloride and extraction with ethyl acetate. The organic layerwas washed with water and then concentrated under reduced pressure. Theresidue thus obtained was subjected to silica gel column chromatographyfor separation and purification. Elution with dichloromethane-methanol(50:1) yielded 829 mg (2.87 mmol) of1-chloro-4-(α-hydroxyisopropyl)-2-(2-methoxyethoxymethoxymethyl)benzene.

To 829 mg (2.87 mmol) of the above-obtained hydroxy compound were added5.0 ml of ether, 30 ml of a 50% aqueous solution of hydrogen peroxideand 0.2 ml of concentrated sulfuric acid, and the mixture was allowed toreact at room temperature for 17 hours. To the reaction mixture wasadded water followed by extraction with ethyl acetate. The organic layerwas washed with water and then concentrated under reduced pressure. Theresidue thus obtained was subjected to silica gel column chromatographyfor separation and purification. Elution with ethyl acetate-hexane (3:1)yielded 699 mg (2.18 mmol) of1-chloro-4-(α-hydroperoxyisopropyl)-2-(2-methoxyethoxymethoxymethyl)benzene.

NMR (ppm, CDCl₃)

8.21(s, 1 H), 7.41-7.08(s, 3 H), 4.73(s, 2 H),

4 52(s, 2 H), 3.82-3.43(m, 4 H), 3.35(s, 3 H),

1.56(s, 6 H).

IR(νcm⁻¹,CHCl₃) 3530, 3330.

EXAMPLE 13

[4-(α-Hydroperoxyisopropyl)-2-methyl]benzyl benzyl ether ##STR36##

To a solution of 298 mg (7.46 mmol) of sodium hydride contained at 60%in mineral oil in dry dimethylformamide (20 ml) was added 1.00 g (4.97mmol) of 4-bromo-2-methylbenzyl alcohol in an atmosphere of argon, andthe mixture was allowed to react at 40 -50° C. for 30 min. To thereaction mixture was added 1.02 g (5.96 mmol) of benzyl bromide, and themixture was reacted at room temperature for 17 hours. To the reactionsolution at 0° C. was added a saturated aqueous solution of ammoniumchloride followed by extraction with ethyl acetate. The organic layerwas washed with water and then concentrated under reduced pressure. Theresidue thus obtained was subjected to silica gel column chromatographyfor separation and purification. Elution with ethyl acetate-hexane (1:3)yielded 1.26 g (4.32 mmol) of (4-bromo-2-methyl)benzyl benzyl ether.

To a solution of 1.26 g (4.32 mmol) of the above-obtained compound indry tetrahydrofuran (20 ml) at -78° C. was added 1.60M hexane solutionof n-butyllithium (3.24 ml, 5.18 mmol) in the atmosphere of argon, andthe mixture was allowed to react for 30 min. To the solution was added5.0 ml (68.0 mmol) of acetone and the mixture was allowed to react at-78° C. for 10 min. To the solution was added a saturated aqueoussolution of ammonium chloride followed by extraction with ethyl acetate.The organic layer was washed with water and then concentrated underreduced pressure. The residue thus obtained was subjected to silica gelcolumn chromatography for separation and purification. Elution withdichloromethane-methanol (100:1) yielded 898 mg (3.32 mmol) of[4-(α-hydroxyisopropyl)-2-methyl]benzyl benzyl ether.

To 898 mg (3.32 mmol) of the above-obtained hydroxy compound were added5.0 ml of ether, 30 ml of a 50% aqueous solution of hydrogen peroxideand 0.2 ml of concentrated sulfuric acid, and the mixture was allowed toreact at room temperature for 17 hours. To the reaction mixture wasadded water followed by extraction with ethyl acetate. The organic layerwas washed with water and then concentrated under reduced pressure. Theresidue thus obtained was subjected to silica gel column chromatographyfor separation and purification. Elution of ethyl acetate-hexane (1:4)yielded 783 mg (2.59 mmol) of[4-(α-hydroperoxyisopropyl)-2-methyl]benzyl benzyl ether.

NMR (ppm, CDCl₃)

8.22(br, 1 H), 7.51-7.18(m, 8 H), 4.48(s, 4 H),

2.26(s, 3 H), 1.57(s, 6 H).

IR(νcm⁻¹,CHCl₃) 3530, 3320.

EXAMPLE 14

4-(α-Hydroperoxyisopropyl)-2,6-dichlorobenzyl benzyl ether ##STR37##

To a solution of 336 mg (8.39 mmol) of sodium hydride contained at 60%in mineral oil in dry dimethylformamide (30 ml) was added 1.43 g (5.59mmol) of 4-bromo-2,6-dichloro-benzyl alcohol in an atmosphere of argon,and the mixture was allowed to react at 40°-50° C. for 30 min. To thereaction mixture was added 1.15 g (6.71 mmol) of benzyl bromide, and themixture was allowed to react at room temperature for 18 hours. To thereaction solution at 0° C. was added a saturated aqueous solution ofammonium chloride followed by extraction with ethyl acetate. The organiclayer was washed with water and then concentrated under reducedpressure. The residue thus obtained was subjected to silica gel columnchromatography for separation and purification. Elution withdichloromethane-hexane (1:1) yielded 1.68 g (4.86 mmol) of(4-bromo-2,6-dichloro)benzyl benzyl ether.

To a solution of 1.68 g (4.86 mmol) of the above-obtained compound indry tetrahydrofuran (40 ml) at -78° C. was added 1.60M hexane solutionof n-butyllithium (3.65 ml, 5.83 mmol) in the atmosphere of argon, andthe mixture was allowed to react for 30 min. To the solution was added5.00 ml (68.1 mmol) of acetone, and the mixture was reacted at -78° C.for 10 min. followed by addition of a saturated aqueous solution ofammonium chloride and extraction with ethyl acetate. The organic layerwas washed with water and then concentrated under reduced pressure. Theresidue obtained was then subjected to silica gel column chromatographyfor separation and purification. Elution with dichloromethanemethanol(100:1) yielded 1.17 g (3.59 mmol) of[2.6-dichloro-4-(a-hydroxyisopropyl)benzyl]benzyl ether.

To 1.17 g (3.59 mmol) of the above-obtained hydroxy compound were added5 ml of ether, 20 ml of a 30% aqueous solution of hydrogen peroxide and0.50 ml of concentrated sulfuric acid. The mixture was allowed to reactat room temperature for 18 hours followed by addition of water andextraction with ethyl acetate. The organic layer was washed with water.The residue obtained was then subjected to silica gel columnchromatography for separation and purification. Elution withdichloromethane-methanol (100:1) yielded 870 mg (2.55 mmol) of4-(α-hydroperoxyisopropyl)-2,6-dichlorobenzyl benzyl ether.

NMR (ppm, CDCl₃)

7.95 (s, 1 H), 7.3-7.06 (m, 7 H), 4.53 (s, 4 H),

1.57 (s, 6 H).

IR(νcm⁻¹,CHCl₃) 3530, 3330.

EXAMPLE 15

1-[4- -Hydroperoxyisopropyl)benzenesulfonyl]butane ##STR38##

To a solution of 2.92 g (15.9 mmol) of 1-iodated butane in drydichloromethane (30 ml) were added 5.34 g (52.9 mmol) of triethylamineand 1.50 g (13.2 mmol) of 4-bromothiophenol in an atmosphere of argon,and the mixture was allowed to react at room temperature for 18 hours.To the solution was added water followed by extraction with ethylacetate. The organic layer was washed with water and then concentratedunder reduced pressure. The residue thus obtained was subjected tosilica gel column chromatography for separation and purification.Elution with dichloromethane-hexane (1:4) yielded 3.28 g (12.8 mmol) of4-bromophenyl butyl sulfide.

To a solution of 3.28 g (12.8 mmol) of the above-obtained compound indry tetrahydrofuran (30 ml) at -78° C. was added 1.60M hexane solutionof n-butyllithium (9.63 ml, 15.4 mmol) in the atmosphere of argon, andthe mixture was allowed to react for 30 min. To the solution was added4.0 ml (54.5 mmol) of acetone, and the mixture was reacted at -78° C.for 10 min. followed by addition of a saturated aqueous solution ofammonium chloride and extraction with ethyl acetate. The organic layerwas washed with water and then concentrated under reduced pressure. Theresidue thus obtained was subjected to silica gel column chromatographyfor separation and purification. Elution with dichloromethane-methanol(100:1) yielded 2.32 g (9.85 mmol) of 4-(α-hydroxyisopropyl)phenyl butylsulfide.

To 2.32 g (9.85 mmol) of the above-obtained hydroxy compound were added20 ml of ether, 20 ml of a 30% aqueous solution of hydrogen peroxide and0.50 ml of concentrated sulfuric acid. The mixture was allowed to reactat room temperature for 16 hours followed by addition of water andextraction with ethyl acetate. The organic layer was washed with waterand then concentrated under reduced pressure. The residue thus obtainedwas subjected to silica gel column chromatography for separation andpurification. Elution with ethyl acetate-hexane (3:1) yielded 1.83 g(7.27 mmol) of 1-[4-(α-hydroperoxyisopropyl)benzenesulfonyl]butane.

NMR (ppm, CDCl₃)

7.83(s, 1 H), 7.72-7.13(m, 4 H), 4.03-3.75

(m, 2 H), 1.60(s, 6 H), 1.37-0.82(m, 7 H).

IR(νcm³¹ 1,CHCl₃) 3400.

EXAMPLE 16

N,N-Dimethyl[4-(α-hydroperoxyisopropyl)benzene]sulfoamide ##STR39##

To a solution of 2.92 g (35.8 mmol) of dimethylamine hydrochloride in 50ml of dry pyridine was added 5.20 g (20.4 mmol) of4-bromobenzenesulfonyl chloride in an atmosphere of argon, and themixture was allowed to react at 0° C. for 2 hours. To the solution wasadded water followed by extraction with ethyl acetate. The organic layerwas washed with water and then concentrated under reduced pressure. Theresidue thus obtained was subjected to silica gel column chromatographyfor separation and purification. Elution with dichloromethane yielded5.01 g (19.0 mmol) of N,N-dimethyl-(4-bromobenzene)sulfoamide.

To a solution of 5.01 g (19.0 mmol) of the above-obtained compound in 50ml of dry tetrahydrofuran at -78° C. was added 1.60M hexane solution ofn-butyllithium (15.0 ml, 24.0 mmol) in the atmosphere of argon, and themixture was allowed to react for 30 min. To the solution was added 6.0ml (81.7 mmol) of acetone, and the mixture was reacted at -78° C. for 10min. followed by addition of a saturated aqueous solution of ammoniumchloride and extraction with ethyl acetate. The organic layer was washedwith water and then concentrated under reduced pressure. The residuethus obtained was subjected to silica gel column chromatography forseparation and purification. Elution with ethyl acetatehexane (1:2)yielded 3.42 g (14.1 mmol) ofN,N-dimethyl-[4-(α-hydroxyisopropyl)benzene]sulfoamide.

To 3.42 g (14.1 mmol) of the above-obtained hydroxy compound were added20 ml of ether, 20 ml of a 30% aqueous solution of hydrogen peroxide and0.500 ml of concentrated sulfuric acid. The mixture was allowed to reactat room temperature for 16 hours followed by addition of water andextraction with ethyl acetate. The organic layer was washed with waterand then concentrated under reduced pressure. The residue thus obtainedwas subjected to silica gel column chromatography for separation andpurification. Elution with dichloromethane-methanol (50:1) yielded 2.71g (10.5 mmol) ofN,N-dimethyl-[4-(α-hydroperoxyisopropyl)benzene]sulfoamide.

NMR (ppm, CDCl₃)

7.83-7.10(m, 4 H), 7.67(s, 1 H), 2.75(s, 6 H),

1.66(s, 6 H).

IR(νcm⁻¹,CHCl₃) 3400.

EXAMPLE 17

[4-(α-Hydroperoxyisopropyl)benzene]sulfonyl-3,5,8-trioxanonane ##STR40##

To a solution of 1.20 g (6.35 mmol) of 4-bromothiophenol in drytetrahydrofuran (30 ml) was added 1.62 g (7.62 mmol) of1-bromo-3,5,8-trioxanonane in an atmosphere of argon, and the mixturewas allowed to react at room temperature for 24 hours. To the solutionwas added water followed by extraction with ethyl acetate. The organiclayer was washed with water and then concentrated under reducedpressure. The residue thus obtained was subjected to silica gel columnchromatography for separation and purification. Elution withdichloromethane yielded 1.92 g (5.97 mmol) of4-bromophenyl-2-(2-methoxyethoxymethoxy)ethyl sulfide.

To a solution of 1.92 g (5.97 mmol) of the above-obtained compound indry tetrahydrofuran (30 ml) at -78° C. was added 1.60M hexane solutionof n-butyllithium (4.5 ml, 7.16 mmol) in the atmosphere of argon, andthe mixture was allowed to react for 30 min. To the solution was added4.0 ml (54.5 mmol) of acetone, and the mixture was reacted at -78° C.for 10 min. followed by addition of a saturated aqueous solution ofammonium chloride and extraction with ethyl acetate. The organic layerwas washed with water and then concentrated under reduced pressure. Theresidue thus obtained was subjected to silica gel column chromatographyfor separation and purification. Elution with dichloromethane-methanol(50:1) yielded 1.33 g (4.42 mmol) of 4-(α-hydroxyisopropyl)phenyl2-(2-methoxyethoxymethoxy)ethyl sulfide.

To 1.33 g (4.42 mmol) of the above-obtained hydroxy compound were added10 ml of ether, 20 ml of a 30% aqueous solution of hydrogen peroxide and0.50 ml of concentrated sulfuric acid, and the mixture was allowed toreact at room temperature for 18 hours followed by addition of water andextraction with ethyl acetate. The organic layer was washed with waterand then concentrated under reduced pressure. The residue thus obtainedwas subjected to silica gel column chromatography for separation andpurification. Elution with ethyl acetate-hexane (3:1) yielded 1.16 g(3.32 mmol) of1-[4-(α-hydroperoxyisopropyl)benzene]sulfonyl-3,5,8-trioxanonane.

NMR (ppm, CDCl₃)

7.93 (s, 1 H), 7.43-7.01 (m, 4 H), 4.68 (s, 2 H),

4.88-3.77 (m, 8 H), 3.34 (s, 3 H), 1.62 (s, 6 H).

IR(νcm⁻¹,CHCl₃) 3520, 3330.

EXAMPLE 18

N-[4-(α-Hydroperoxyisopropyl)benzenesulfonyl]morpholine ##STR41##

To a solution of 1.67 g (19.14 mmol) of morpholine in 50 ml of drypyridine was added 3.26 g (12.76 mmol) of 4-bromobenzenesulfonylchloride in an atmosphere of argon, and the mixture was allowed to reactat 0° C for 3 hours. To the solution was added water followed byextraction with ethyl acetate. The organic layer was washed with waterand then concentrated under reduced pressure. The residue thus obtainedwas subjected to silica gel column chromatography for separation andpurification. Elution with dichloromethane yielded 3.45 g (11.3 mmol) ofN-(4-bromobenzenesulfonyl)morpholine.

To a solution of 3.45 g (11.3 mmol) of the above-obtained compound in 50ml of dry tetrahydrofuran at -78° C. was added 1.60M hexane solution ofn-butyllithium (8.5 ml, 13.6 mmol) in the atmosphere of argon, and themixture was allowed to react for 30 min. To the solution was added 4.0ml (54.5 mmol) of acetone, and the mixture was reacted at -78° C. for 10min. followed by addition of a saturated aqueous solution of ammoniumchloride and extraction with ethyl acetate. The organic layer was washedwith water and then concentrated under reduced pressure. The residuethus obtained was subjected to silica gel column chromatography forseparation and purification. Elution with ethyl acetatehexane (1:2)yielded 2.49 g (8.37 mmol) ofN-[4-(α-hydroxyisopropyl)benzenesulfonyl]morpholine.

To 2.49 g (8.37 mmol) of the above-obtained hydroxy compound were added20 ml of ether, 20 ml of a 30% aqueous solution of hydrogen peroxide and0.500 ml of concentrated sulfuric acid. The mixture was allowed to reactat room temperature for 17 hours followed by addition of water andextraction with ethyl acetate. The organic layer was washed with waterand then concentrated under reduced pressure. The residue thus obtainedwas subjected to silica gel column chromatography for separation andpurification. Elution with dichloromethane-methanol (50:1) yielded 1.99g (6.35 mmol) ofN-[4-(α-hydroperoxyisopropyl)benzenesulfonyl]morpholine.

NMR (ppm, CDCl₃)

7.80 (s, 1 H), 7.79-7.08 (m, 4 H), 3.83-3.60

(m, 4 H) 3.10-2.87 (m, 4 H), 1.58 (s, 6 H).

IR(νcm⁻¹,KBr) 3400.

EXAMPLE 19

1,3-Bis[4-(α-hydroperoxyisopropyl)phenyl]propane ##STR42##

To a solution of 3.40 g (17.1 mmol) of 4'-bromoacetophenone in ethanol(140 ml) was added 3.80 g (20.5 mmol) of 4-bromobenzaldehyde followed byfurther addition at 0° C. of an aqueous solution of 4.19 g (105 mmol) ofsodium hydroxide (14 ml). The mixture was allowed to react at roomtemperature for one hour, then precipitates formed were collected byfiltration and washed with cooled dichloromethane. There was obtained5.30 g (14.5 mmol) of the crystals.

To a solution of 5.30 g (14.5 mmol) of the above-obtained compound intoluene (50 ml) was added 1.20 g of palladium-on-carbon, and the mixturewas vigorously stirred in an atmosphere of hydrogen. The reaction wascarried out at room temperature for 6 hours, then insoluble matter wasremoved by filtration, and the solution thus obtained was concentratedunder reduced pressure.

To 4.68 g of the compound thus obtained was added methanol (100 ml)followed by addition at 0° C. of 1.53 g (40.4 mmol) of sodiumborohydride. The mixture was allowed to react at room temperature for 3hours. To the solution was added water followed by extraction with ethylacetate. The organic layer was washed with water and then concentratedunder reduced pressure. To 4.51 g of the compound thus obtained wasagain added toluene (50 ml) followed by addition of 1.05 g ofpalladium-on-carbon. The mixture was vigorously stirred in theatmosphere of hydrogen. The reaction was carried out at room temperaturefor 10 hours, insoluble matter was removed by filtration, and thesolution thus obtained was concentrated under reduced pressure. Theresidue thus obtained was subjected to silica gel column chromatographyfor separation and purification. There was produced 692 mg (1.95 mmol)of 1,3-bis(4-bromophenyl)propane.

Next, to a solution of 692 mg (1.95 mmol) of the above-obtained compoundin dry tetrahydrofuran (14 ml) at -78° C. was added a 1.60M hexanesolution of a n-butyllithium (3.00 ml, 4.80 mmol), and the mixture wasallowed to react for 30 min. To the solution was added 1.50 ml (20.4mmol) of acetone, and the mixture was reacted at -78° C. for 10 min.followed by addition of a saturated aqueous solution of ammoniumchloride and extraction with ethyl acetate. The organic layer was washedwith water and then concentrated under reduced pressure. The residuethus obtained was subjected to silica gel column chromatography forseparation and purification. Elution with dichloromethane-methanol(25:1) yielded 505 mg (1.62 mmol) of1,3-bis[4-(α-hydroxyisopropyl)phenyl]propane.

To 505 mg (1.62 mmol) of the above-obtained compound were added 5 ml ofether, 10 ml of a 30% aqueous solution of hydrogen peroxide and 0.25 mlof concentrated sulfuric acid. The mixture was allowed to react at roomtemperature for 18 hours followed by addition of water and extractionwith ethyl acetate. The organic layer was washed with water and thenconcentrated under reduced pressure. The residue thus obtained wassubjected to silica gel column chromatography for separation andpurification. Elution with ethyl acetate-hexane (1:1) yielded 510 mg(1.48 mmol) of 1,3-bis[4-(α-hydroperoxyisopropyl)phenyl]propane.

NMR (ppm, CDCl₃)

8.05(s, 2 H), 7.36-7.02 (m, 8 H), 2.63-

2.31(m, 4 H), 2.14-1.86(m, 2 H), 1.53(s, 12 H).

IR(νcm⁻¹,CHCl₃) 3530, 3330.

EXAMPLE 20

2,2-Bis[4-(α-hydroperoxyisopropyl)phenyl]-3,5,8-trioxanonane ##STR43##

To a solution of 6.43 g (18.1 mmol) of 1,1-bis(4-bromophenyl)ethanol indry dichloromethane (50 ml) were added 2.50 ml (21.9 mmol) ofβ-methoxyethoxymethyl chloride and 4.8 ml (27.6 mmol) ofN,N-diisopropylethylamine in an atmosphere of argon, and the mixture wasrefluxed for 15 hours.

To the solution was added water followed by extraction withdichloromethane. The organic layer was washed with water andconcentrated under reduced pressure. The residue thus obtained wassubjected to silica gel column chromatography for separation andpurification. Elution with dichloromethane yielded 6.55 g (14.8 mmol) of2,2-bis-(4-bromophenyl)-3,5,8-trioxanonane.

To a solution of 6.55 g (14.8 mmol) of the above-obtained compound indry tetrahydrofuran (200 ml) at -78° C. was added a 1.60M hexanesolution of n-butyllithium (23.0 ml, 36.8 mmol) in the atmosphere ofargon, and the mixture was allowed to react for 30 min. To the solutionwas added 11.0 ml (150 mmol) of acetone, and the mixture was allowed toreact at -78° C. for 10 min. followed by addition of a saturated aqueoussolution of ammonium chloride and extraction with ethyl acetate. Theorganic layer was washed with water and then concentrated under reducedpressure. The residue thus obtained was subjected to silica gel columnchromatography for separation and purification. Elution withdichloromethane-methanol (50:1) yielded 4.67 g (11.6 mmol) of2,2-bis-[4-(α-hydroxyisopropyl)phenyl-3,5,8-trioxanonane.

To 4.67 g (11.6 mmol) of the above-obtained hydroxy compound were added20 ml of ether, 40 ml of 30% aqueous solution of hydrogen peroxide and1.00 ml of concentrated sulfuric acid. The mixture was allowed to reactat room temperature for 16 hours followed by addition of water andextraction with ethyl acetate. The organic layer was washed with waterand then concentrated under reduced pressure. The residue thus obtainedwas subjected to silica gel column chromatography for separation andpurification. Elution with ethyl acetate-hexane (1:1) yielded 4.08 g(9.40 mmol) of2,2-[bis4-(α-hydroperoxyisopropyl)phenyl]-3,5,8-trioxanonane.

NMR (ppm, CDCl₃)

8.05(s, 2 H), 7.51-7.22(m, 8 H), 4.68(s, 2 H),

3.33(m, 4 H), 3.32(s, 3 H), 1.92(s, 3 H),

1.51(s, 12 H)

IR(νcm⁻¹,CHCl₃) 3530, 3320

EXAMPLE 21

1,7-Bis[4-(α-hydroperoxyisopropyl)phenyl]-4-hydroxyheptane ##STR44##

To a solution of 3.06 g (80.5 mmol) of lithium aluminum hydride in drydiethyl ether (150 ml) at 0° C. was added 4.13 g (17.9 mmol) of diethyl4-oxopimerate in an atmosphere of argon, and the mixture was allowed toreact at room temperature for 18 hours. To the reaction mixture cooledto 0° C. was added saturated aqueous solution of ammonium chloride, andprecipitates formed were removed by filtration. The solution thusobtained was concentrated under reduced pressure, and the residue wassubjected to silica gel column chromatography for separation andpurification.

Elution with dichloromethane-methanol (5:1) yielded 1.62 g (10.9 mmol)of 1,4,7-heptatriol.

To a solution of 1.62 g (10.9 mmol) of the above-obtained compound indry pyridine (100 ml) was added 4.57 g (24.0 mmol) of p-toluenesulfonylchloride at room temperature in the atmosphere of argon, and the mixturewas allowed to react for 20 hours.

To the solution was added water followed by extraction withdichloromethane. The organic layer was washed with water andconcentrated under reduced pressure. The residue thus obtained wassubjected to silica gel column chromatography for separation andpurification. Elution with dichloromethane-methanol (100:1) yielded 3.58g (7.85 mmol) of 1,7-bis(p-toluenesulfoxy)-4-heptanol.

To a solution of 3.58 g (7.85 mmol) of the above-obtained compound indry dimethylformamide (100 ml) were added 2.39 g (8.70 mmol) oftert-butyldiphenylsilyl chloride and 1.42 g (20.8 mmol) of imidazole,and the mixture was allowed to react at room temperature for 8 hours. Tothe solution was added water followed by extraction with benzene. Theorganic layer was washed with water and concentrated under reducedpressure. The residue thus obtained was subjected to silica gel columnchromatography for separation and purification. From the eluate withdichloromethanehexane (1:1) was afforded 4.74 g (6.85 mmol) of1,7-bis(p-toluenesulfoxy)-4-(tert-butyldiphenylsiloxy)heptane.

To a solution of 4.74 g (6.85 mmol) of the above-obtained compound inacetone (200 ml) was added 4.18 g (27.9 mmol) of sodium iodide, and themixture was refluxed for 18 hours. To the solution was added waterfollowed by extraction with benzene. The organic layer was washed withwater and concentrated under reduced pressure. The residue thus obtainedwas subjected to silica gel column chromatography for separation andpurification. From the eluate with dichloromethane-hexane (1:5) wasafforded 3.44 g (5.68 mmol) of1,7-diiodo-4-(tert-butyldiphenylsiloxy)heptane.

To a solution of 3.42 g (14.5 mmol) of 1,4-dibromobenzene in drytetrahydrofuran (100 ml) at -78° C. was added a 1.60M hexane solution ofn-butyllithium (9.10 ml, 14.6 mmol) in the atmosphere of argon, and themixture was allowed to react for 30 min. To the solution was added asolution of 3.44 g (5.68 mmol) of1,7-diiodo-4-(tert-butyldiphenylsiloxy)heptane previously produced indry tetrahydrofuran (35 ml). The temperature was raised from -78° C. toroom temperature over 9 hours, and the reaction was allowed to proceedat room temperature for 15 hours. To the reaction mixture was added asaturated aqueous solution of ammonium chloride followed by extractionwith benzene. The organic layer was washed with water and concentratedunder reduced pressure. The residue thus obtained was subjected tosilica gel column chromatography for separation and purification. Fromthe eluate with dichloromethane-hexane (1:5) was afforded 1.05 g (1.58mmol) of 1,7-bis(4-bromophenyl)- 4-(tert-butyldiphenylsiloxy)-heptane

Further, to a solution of 1.05 g (1.58 mmol) of1,7-bis(4-bromophenyl)-4-(tert-butyldiphenylsiloxy)heptane in drytetrahydrofuran (50 ml) was added a 1.60M hexane solution ofn-butyllithium (2.15 ml, 3.44 mmol) in the atmosphere of argon, and themixture was allowed to react at -78° C. for 30 min. To the solution wasadded 1.20 ml (16.3 mmol) of acetone, and the mixture was reacted at-78° C. for 10 min. followed by addition of a saturated aqueous solutionof ammonium chloride and extraction with ethyl acetate. The organiclayer was washed with water and concentrated under reduced pressure. Theresidue thus obtained was subjected to silica gel column chromatographyfor separation and purification. Elution with dichloromethane-methanol(100:1) yielded 728 mg (1.23 mmol) of1,7-bis[4-(α-hydroxyisopropyl)phenyl]-4-(tert-butyldiphenylsiloxy)heptane.

Next, to 728 mg (1.23 mmol) of the above-obtained compound were added 5ml of ether, 10 ml of a 30% aqueous solution of hydrogen peroxide and0.25 ml of concentrated sulfuric acid. The mixture was allowed to reactat room temperature for 16 hours followed by addition of water andextraction with ethyl acetate. The organic layer was washed with waterand then concentrated under reduced pressure. The residue thus obtainedwas subjected to silica gel column chromatography for separation andpurification. Elution with ethyl acetate-hexane (1:2) yielded 658 mg(1.06 mmol) of1,7-bis[4-(α-hydroperoxyisopropyl)phenyl]-4-(tert-butyldiphenylsiloxy)heptane.

Further, to a solution of 658 mg (1.06 mmol) of the above-obtainedcompound in dry tetrahydrofuran (20 ml) was added a 1.0M tetrahydrofuransolution of tetrabutylammonium fluoride (2.50 ml, 2.5 mmol), and themixture was allowed to react at room temperature for 6 hours. To thesolution was added water followed by extraction with ethyl acetate. Theorganic layer was washed with water and concentrated under reducedpressure. The residue thus obtained was subjected to silica gel columnchromatography for separation and purification. Elution withdichloromethane-methanol (50:1) yielded 406 mg (0.976 mmol) of1,7-bis[4-(α-hydroperoxyisopropyl)phenyl]-4-hydroxyheptane.

NMR (ppm, CDCl₃)

8.11(s, 2 H) 7.39-7.05(m 8 H) 3.66-3.28(m,

1 H), 2.59-2.24(m, 4 H), 2.11-1.82(m, 8 H).

IR (νcm⁻¹, CHCl₃) 3600, 3530, 3400.

EXAMPLE 22

Bis[4-(α-hydroperoxyisopropyl)benzyl]ether ##STR45##

To a solution of 27.4 g (685 mmol) of sodium hydride contained at 60% inmineral oil in dry dimethylformamide (425 ml) was added 42.4 g (227mmol) of 4-bromobenzyl alcohol in an atmosphere of argon, and themixture was allowed to react at 40-50° C. for 30 min. Then, 62.4 g (250mmol) of 4-bromobenzyl bromide was added, and the mixture was reacted atroom temperature for 15 hours. The reaction mixture was added to icewater, and the mixture was extracted with ethyl acetate. The organiclayer was washed with water and concentrated under reduced pressure. Theresidue thus obtained was subjected to silica gel column chromatographyfor separation and purification. Elution with dichloromethane-hexane(1:1) yielded 72.7 g (204 mmol) of 4-bromobenzyl ether.

To a solution of 4.73 g (13.3 mmol) of the above-obtained compound indry tetrahydrofuran (100 ml) at -78° C. was added a 1.60M hexanesolution of n-butyllithium (21.0 ml, 33.6 mmol) in the atmosphere ofargon, and the mixture was allowed to react for 30 min. To the solutionwas added 10.0 ml (136 mmol) of acetone, and the mixture was reacted at-78° C. for 10 min. followed by addition of a saturated aqueous solutionof ammonium chloride and extraction with ethyl acetate. The organiclayer was washed with water and then concentrated under reducedpressure. The residue thus obtained was subjected to silica gel columnchromatography for separation and purification. Elution withdichloromethane-methanol (100:1) yielded 3.30 g (10.5 mmol) of4-(α-hydroxyisopropyl)benzyl ether.

To 3.30 g (10.5 mmol) of the above-obtained hydroxy compound were added15 ml of ether, 30 ml of a 30% aqueous solution of hydrogen peroxide and0.75 ml of concentrated sulfuric acid. The mixture was allowed to reactat room temperature for 16 hours followed by addition of water andextraction with ethyl acetate. The organic layer was washed with waterand concentrated under reduced pressure. The residue thus obtained wassubjected to silica gel column chromatography for separation andpurification. Elution with ethyl acetate-hexane (1:2) yielded 3.35 g(9.67 mmol) of bis[4-(α-hydroperoxyisopropyl)benzyl]ether.

NMR (ppm, CDCl₃)

8.00(s, 2 H), 7.45-7.13(m, 8 H), 4.47(s, 4 H)

1.53(s, 12 H).

IR (νcm⁻¹, CHCl₃) 3530, 3330.

EXAMPLE 23

1,12-Bis[4-(α-hydroperoxyisopropyl)phenyl]-2,5,8,11-tetraoxadodecane##STR46##

To a solution of 355 mg (8.88 mmol) of sodium hydride contained at 60%in mineral oil in dry dimethylformamide (60 ml) was added 851 mg (5.67mmol) of triethylene glycol in an atmosphere of argon, and the mixturewas reacted at 40°-50° C. for 30 min. followed by addition of 3.37 g(13.5 mmol) of 4-bromobenzyl bromide. The mixture was allowed to reactat room temperature for 18 hours. To the reaction mixture at 0° C. wasadded a saturated aqueous solution of ammonium chloride followed byextraction with ethyl acetate. The organic layer was washed with waterand then concentrated under reduced pressure. The residue thus obtainedwas subjected to silica gel column chromatography for separation andpurification. Elution with dichloromethane yielded 2.51 g (5.14 mmol) of1,12-bis(4-bromophenyl)-2,5,8,11-tetraoxadodecane.

To a solution of 2.51 g (5.14 mmol) of the above-obtained compound indry tetrahydrofuran (50 ml) at -78° C. was added a 1.60M hexane solutionof n-butyllithium (8.00 ml, 12.8 mmol) in the atmosphere of argon, andthe mixture was allowed to react for 30 min. To the solution was added4.00 ml (54.5 mmol) of acetone, and the mixture was reacted at -78° C.for 10 min. followed by addition of a saturated aqueous solution ofammonium chloride and extraction with ethyl acetate. The organic layerwas washed with water and then concentrated under reduced pressure. Theresidue thus obtained was subjected to silica gel column chromatographyfor separation and purification.

Elution with dichloromethane-methanol (25:1) yielded 1.99 g (4.42 mmol)of 1,12-bis[4-(α-hydroxyisopropyl)phenyl]-2,5,8,11-tetraoxadodecane.

To 1.99 g (4.42 mmol) of the above-obtained hydroxy compound were added10 ml of ether, 20 ml of a 30% aqueous solution of hydrogen peroxide and0.50 ml of concentrated sulfuric acid. The mixture was allowed to reactat room temperature for 15 hours followed by addition of water andextraction with ethyl acetate. The organic layer was washed with waterand then concentrated under reduced pressure. The residue thus obtainedwas subjected to silica gel column chromatography for separation andpurification. Elution with ethyl acetate-hexane (2:1) yielded 1.84 9(3.82 mmol) of1,12-bis[4-(α-hydroperoxyisopropyl)phenyl]-2,5,8,11-tetraoxadodecane.

NMR (ppm, CDCl₃)

7.93(s, 2 H), 7.47-7.17(m, 8 H), 4.50(s, 4 H),

3.61(s, 12 H), 1.53(s, 12 H).

IR (νcm⁻¹, CHCl₃) 3530, 3330.

EXAMPLE 24

1,21-Bis[4-(α-hydroperoxyisopropyl)phenyl]-2,5,8,11,14,17,20-heptaoxaheneicosane##STR47##

To a solution of 766 mg (19.2 mmol) of sodium hydride contained at 60%in mineral oil in dry dimethylformamide (40 ml) was added 1.80 g (6.38mmol) of hexaethylene glycol in an atmosphere of argon, and the mixturewas allowed to react at 40°-50° C. for 30 min. Then, 3.51 g (14.0 mmol)of 4-bromobenzyl bromide was added, and the mixture was allowed to reactat room temperature for 16 hours. To the reaction mixture at 0° C. wasadded a saturated aqueous solution of ammonium chloride followed byextraction with ethyl acetate. The organic layer was washed with waterand then concentrated under reduced pressure. The residue thus obtainedwas subjected to silica gel column chromatography for separation andpurification. Elution with dichloromethane yielded 3.64 g (5.87 mmol) of1,21-bis(4-bromophenyl)-2,5,8,11,14,17,20-heptaoxaheneicosane.

To a solution of 3.64 g (5.87 mmol) of the above-obtained compound indry tetrahydrofuran (70 ml) at -78° C. was added a 1.60M hexane solutionof n-butyllithium (9.20 ml, 14.7 mmol) in the atmosphere of argon, andthe mixture was allowed to react for 30 min. To the solution was added4.40 ml (59.9 mmol) of acetone, and the mixture was reacted at -78° C.for 10 min. followed by addition of a saturated aqueous solution ofammonium chloride and extraction with ethyl acetate. The organic layerwas washed with water and then concentrated under reduced pressure. Theresidue thus obtained was subjected to silica gel column chromatographyfor separation and purification. Elution with dichloromethane-methanol(25:1) yielded 2.82 g (4.87 mmol) of1,21-bis[4-(α-hydroxyisopropyl)phenyl]-2,5,8,11,14,17,20-heptaoxaheneicosane.

To 2.82 g (4.87 mmol) of the above-obtained hydroxy compound were added10 ml of ether, 20 ml of a 30% aqueous solution of hydrogen peroxide and0.50 ml of concentrated sulfuric acid. The mixture was allowed to reactat room temperature for 18 hours followed by addition of water andextraction with ethyl acetate. The organic layer was washed with waterand then concentrated under reduced pressure. The residue thus obtainedwas subjected to silica gel column chromatography for separation andpurification. Elution with ethyl acetate-hexane (2:1) yielded 2.71 g(4.44 mmol) of1,21-bis[4-(α-hydroperoxyisopropyl)phenyl]-2,5,8,11,14,17,20-heptaoxaheneicosane.

NMR (ppm, CDCl₃)

8.07(bs, 2 H), 7.50-7.17(m, 8 H), 4.52(s, 4 H),

3.63(s, 24 H), 1.57(s, 12 H).

IR (νcm⁻¹, CHCl₃) 3530, 3340.

EXAMPLE 25

Bis-[4-(α-hydroperoxyisopropyl)phenyl]polyethylene glycol ##STR48##

To a solution of 633 mg (15.8 mmol) of sodium hydride contained at 60%in mineral oil in dry dimethylformamide (50 ml) was added 4.06 g (6.76mmol on average) of polyethylene glycol with an average molecular weightof 600 in an atmosphere of argon, and the mixture was allowed to reactat 40°-50° C. for 30 min. Then, 5.12 g (20.4 mmol) of 4-bromobenzylbromide was added, and the mixture was reacted at room temperature for19 hours. To the reaction mixture at 0° C. was added a saturated aqueoussolution of ammonium chloride followed by extraction with ethyl acetate.The organic layer was washed with water and then concentrated underreduced pressure. The residue thus obtained was subjected to silica gelcolumn chromatography for separation and purification. Elution withdichloromethane-methanol (50:1) yielded 2.74 g (3.00 mmol on average) ofa compound having the structure shown below. ##STR49##

To a solution of 2.74 g (3.00 mmol on average) of the above-obtainedcompound in dry tetrahydrofuran (60 ml) at -78° C. was added 1.60Mhexane solution of n-butyllithium (5.70 ml, 9.12 mmol) in the atmosphereof argon, and the mixture was allowed to react for 30 min. To thesolution was added 2.50 ml (34.0 mmol) of acetone, and the mixture wasallowed to react at -78° C. for 10 min. followed by addition of asaturated aqueous solution of ammonium chloride and extraction withethyl acetate. The organic layer was washed with water and thenconcentrated under reduced pressure. The residue thus obtained wassubjected to silica gel column chromatography for separation andpurification. Elution with dichloromethane-methanol (20:1) yielded 1.36g (1.56 mmol on average) of a compound having the formula shown below.##STR50##

To 1.36 g (1.56 mmol on average) of the above-obtained hydroxy compoundwere added 10 ml of ether, 20 ml of a 30% aqueous solution of hydrogenperoxide and 0.50 ml of concentrated sulfuric acid. The mixture wasallowed to react at room temperature for 16 hours followed by additionof water and extraction with ethyl acetate. The organic layer was washedwith water and then concentrated under reduced pressure. The residuethus obtained was subjected to silica gel column chromatography forseparation and purification. Elution with dichloromethane-hexane (20:1)yielded 869 mg (0.961 mmol on average) of a compound having the formulashown below. ##STR51##

NMR (ppm, CDCl₃)

8.09(s, 2 H), 7.48-7.14(m, 8 H), 4.53(s, 4 H),

3.62(s, 52 H), 1.53(s, 12 H).

IR (νcm⁻¹, CHCl₃) 3530, 3330.

EXAMPLE 26

1,14-Bis[4-(α-hydroperoxyisopropyl)phenyl]-2,13-dioxatetradecane##STR52##

To a solution of 851 mg (21.3 mmol) of sodium hydride contained at 60%in mineral oil in dry dimethylformamide (60 ml) was added 1.21 g (6.94mmol) of 1,10-decanediol in an atmosphere of argon, and the mixture wasallowed to react at 40°-50° C. for 30 min. Then, 4.23 g (16.9 mmol) of4-bromobenzyl bromide was added to the solution, and the mixture wasreacted at room temperature for 18 hours. To the solution at 0° C. wasadded a saturated aqueous solution of ammonium chloride followed byextraction with ethyl acetate. The organic layer was washed with waterand then concentrated under reduced pressure. The residue thus obtainedwas subjected to silica gel column chromatography for separation andpurification. Elution with dichloromethane-hexane (1:1) yielded 3.09 g(6.04 mmol) of 1,14-bis(4-bromophenyl)-2,13-dioxatetradecane.

To a solution of 3.09 g (6.04 mmol) of the above-obtained compound indry tetrahydrofuran (80 ml) at -78° C. was added a 1.60M hexane solutionof n-butyllithium (9.40 ml, 15.0 mmol) in the atmosphere of argon, andthe mixture was allowed to react for 30 min. To the solution was added5.00 ml (68.1 mmol) of acetone, and the mixture was reacted at -78° C.for 10 min. followed by addition of a saturated aqueous solution ofammonium chloride and extraction with ethyl acetate. The organic layerwas washed with water and then concentrated under reduced pressure. Theresidue thus obtained was subjected to silica gel column chromatographyfor separation and purification. Elution with dichloromethane-methanol(50:1) yielded 1.10 g (2.34 mmol) of1,14-bis[4-(α-hydroxyisopropyl)phenyl]-2,13-dioxatetradecane.

To 1.10 g (2.34 mmol) of the above-obtained hydroxy compound were added10 ml of ether, 20 ml of a 30% aqueous solution of hydrogen peroxide and0.50 ml of concentrated sulfuric acid. The mixture was allowed to reactat room temperature for 16 hours followed by addition of water andextraction with ethyl acetate. The organic layer was washed with waterand then concentrated under reduced pressure. The residue thus obtainedwas subjected to silica gel column chromatography for separation andpurification. Elution with ethyl acetate-hexane (1:1) yielded 1.04 g(2.07 mmol) of1,14-bis[4-(α-hydroperoxyisopropyl)phenyl]-2,13-dioxatetradecane.

NMR (ppm, CDCl₃)

7.97(bs, 2 H), 7.47-7.10(m, 8 H), 4.40(s, 4 H),

3.40(t, 4H, J=6 Hz), 1.5(s, 12 H), 1.23(bs, 16 H)

IR (νcm⁻¹, CHCl₃) 3530, 3230.

EXAMPLE 27

1,4-Bis[3-(4-(α-hydroperoxyisopropyl)phenyl]-2-oxapropyl]-benzene##STR53##

To a solution of 951 mg (23.8 mmol) of sodium hydride contained at 60%in mineral oil in dry dimethylformamide (50 ml) was added 2.64 g(14.1mmol) of 4-bromobenzyl alcohol in an atmosphere of argon, and themixture was allowed to react at 40°-50° C. for 30 min. Then, 1.62 g(6.14 mmol) of α,α'-dibromo-p-xylene was added, and the mixture wasreacted at room temperature for 19 hours. To the reaction mixture at 0°C. was added a saturated aqueous solution of ammonium chloride followedby extraction with ethyl acetate. The organic layer was washed withwater and then concentrated under reduced pressure. The residue thusobtained was subjected to silica gel column chromatography forseparation and purification. Elution with dichloromethane-hexane (4:1)yielded 1.83 g (3.84 mmol) of1,4-bis[3-(4-bromophenyl)-2-oxapropyl]benzene.

To a solution of 1.83 g (3.84 mmol) of the above-compound in drytetrahydrofuran (60 ml) at -78° C. was added a 1.60M hexane solution ofn-butyllithium (6.00 ml, 9.60 mmol) in the atmosphere of argon, and themixture was allowed to react for 30 min. To the solution was added 3.00ml (40.9 mmol) of acetone, and the mixture was allowed to react at -78°C. for 10 min. followed by addition of a saturated aqueous solution ofammonium chloride and extraction with ethyl acetate. The organic layerwas washed with water and then concentrated under reduced pressure. Theresidue thus obtained was subjected to silica gel column chromatographyfor separation and purification. Elution with dichloromethane-methanol(100:1) yielded 1.22 g (2.81 mmol) of1,4-bis[3-[4-(α-hydroxyisopropyl)phenyl]-2-oxapropyl]-benzene.

To 1.22 g (2.81 mmol) of the above-obtained hydroxy compound were added10 ml of ether, 20 ml of a 30% aqueous solution of hydrogen peroxide and0.500 ml of concentrated sulfuric acid. The mixture was allowed to reactat room temperature for 16 hours followed by addition of water andextraction with ethyl acetate. The organic layer was washed with waterand then concentrated under reduced pressure. The residue thus obtainedwas subjected to silica gel column chromatography for separation andpurification. Elution with ethyl acetate-hexane (1:3) yielded 1.11 g(2.38 mmol) of1,4-bis[3-[4-(α-hydroperoxyisopropyl)phenyl]-2-oxapropyl]benzene.

NMR (ppm, CDCl₃)

8.10(bs, 2 H), 7.48-7.17(m, 12 H), 4.45(s, 8 H),

1.52(s, 12 H).

IR (νcm⁻¹, CHCl₃) 3530, 3330.

EXAMPLE 28

1,13-Bis[4-(α-hydroperoxyisopropyl)phenyl]-7-hydroxy-4,10-dioxatridecane##STR54##

To a solution of 1.22 g (5.97 mmol) of diethyl 3-hydroxyglutarate in drydimethylformamide (30 ml) were added 1.95 g (7.09 mmol) oftert-butyldiphenylsilyl chloride and 1.41 g (20.7 mmol) of imidazole inan atmosphere of argon, and the mixture was allowed to react at roomtemperature for 10 hours. To the solution was added water followed byextraction with benzene. The organic layer was washed with water andconcentrated under reduced pressure. The residue thus obtained wassubjected to silica gel column chromatography for separation andpurification. From the eluate with dichloromethane-hexane (1:1) wasafforded 2.54 g (5.75 mmol) of diethyl3-(tert-butyldiphenylsiloxy)glutarate.

Next, to a solution of 2.54 g (5.75 mmol) of said compound in drydiethyl ether (100 ml) at 0° C. was added 562 mg (14.8 mmol) of lithiumaluminum hydride in the atmosphere of argon, and the mixture was allowedto react at room temperature for 3 hours. To the reaction mixture cooledto 0° C. was added a saturated aqueous solution of ammonium chloride,and precipitates formed were removed by filtration. The solutionobtained was concentrated under reduced pressure, and the residue wassubjected to silica gel column chromatography for separation andpurification. Elution with dichloromethane-methanol (10:1) yielded 1.59g (4.44 mmol) of 3-(tert-butyldiphenylsiloxy)-1,5-pentadiol. Further, toa solution of 1.59 g (4.44 mmol) of the above-obtained compound in drypyridine (100 ml) was added 1.93 g (10.1 mmol) of p-toluenesulfonylchloride, and the mixture was allowed to react at room temperature for18 hours. To the solution was added water followed by extraction withdichloromethane. The organic layer was washed with water andconcentrated under reduced pressure. The residue thus obtained wassubjected to silica gel column chromatography for separation andpurification. Elution with dichloromethane-methanol (100:1) yielded 2.56g (3.84 mmol) of1,5-bis(p-toluenesulfoxy)-3-(tert-butyldiphenylsiloxy)-pentane. Then, toa solution of 635 mg (15.9 mmol) of sodium hydride contained at 60% inmineral oil in dry dimethylformamide (50 ml) was added 2.26 g (10.5mmol) of 3-(4-bromophenyl)-1-propanol in the atmosphere of argon, andthe mixture was allowed to react at 100° C. for 30 min. To the reactionmixture was added 2.56 g (3.84 mmol) of1,5-bis(p-toluenesulfoxy)-3-(tert-butyldiphenylsiloxy)pentane, and themixture was reacted at 100° C. for 16 hours. To the reaction mixture at0° C. was added a saturated aqueous solution of ammonium chloridefollowed by extraction with benzene. The organic layer was washed withwater and then concentrated under reduced pressure. The residue thusobtained was subjected to silica gel column chromatography forseparation and purification. Elution with dichloromethane-hexane (1:2)yielded 1.27 g (1.69 mmol) of1,13-bis(4-bromophenyl)-7-(tert-butyldiphenylsiloxy)-4,10-dioxatridecane.

To a solution of 1.27 g (1.69 mmol) of the above-obtained compound indry tetrahydrofuran (50 ml) at -78° C. was added a 1.60M hexane solutionof n-butyllithium (2.30 ml, 3.68 mmol) in the atmosphere of argon, andthe mixture was allowed to react for 30 min. To the solution was added1.50 ml (20.4 mmol) of acetone, and the mixture was reacted at -78° C.for 10 min. followed by addition of a saturated aqueous solution ofammonium chloride and extraction of ethyl acetate. The organic layer waswashed with water and then concentrated under reduced pressure. Theresidue thus obtained was subjected to silica gel column chromatographyfor separation and purification. Elution with dichloromethane-methanol(50:1) yielded 1.05 g (1.48 mmol) of1,13-bis[4-(α-hydroxyisopropyl)phenyl]-7-(tert-butyldiphenylsiloxy)-4,10-dioxatridecane.

To 1.05 g (1.48 mmol) of the above-obtained hydroxy compound were added10 ml of ether, 20 ml of a 30% aqueous solution of hydrogen peroxide and0.500 ml of concentrated sulfuric acid. The mixture was allowed to reactat room temperature for 12 hours followed by addition of water andextraction with ethyl acetate. The organic layer was washed with waterand then concentrated under reduced pressure. The residue thus obtainedwas subjected to silica gel column chromatography for separation andpurification. Elution with ethyl acetate-hexane (1:1) yielded 1.04 g(1.40 mmol) of1,13-bis[4-(α-hydroperoxyisopropyl)phenyl]-7-(tert-butyldiphenylsiloxy)-4,10-dioxatridecane.

Next, to a solution of 1.04 g (1.40 mmol) of the above-obtained compoundin dry tetrahydrofuran (15 ml) was added 1.0M tetrahydrofuran solutionof tetrabutylammonium fluoride (2.80 ml, 2.80 mmol) in the atmosphere ofargon, and the mixture was allowed to react at room temperature for 6hours. To the solution was added water followed by extraction with ethylacetate. The organic layer was washed with water and then concentratedunder reduced pressure. The residue thus obtained was subjected tosilica gel column chromatography for separation and purification.Elution with dichloromethane-methanol (25:1) yielded 621 mg (1.23 mmol)of1,13-bis[4-(α-hydroperoxyisopropyl)phenyl]-7-hydroxy-4,10-dioxatridecane.

NMR (ppm, CDCl₃)

8.03(s, 2 H), 7.38-7.04(m, 8 H), 3.62-3.31(m,

9 H), 2.59-2.30(m, 4 H), 2.06-1.84(m, 8 H),

1.52(s, 12 H).

IR(νcm⁻¹, CHCl₃) 3600, 3530, 3400.

EXAMPLE 29

1,6-Bis[4-(α-hydroperoxyisopropyl)phenyl]-2,5-dioxahexane ##STR55##

To a solution of 603 mg (15.1 mmol) of sodium hydride contained at 60%in mineral oil in dry dimethylformamide (50 ml) was added 259 mg (4.17mmol) of ethylene glycol in an atmosphere of argon, and the mixture wasallowed to react at 40°-50° C. for 30 min. Then, 2.69 g (10.8 mmol) of4-bromobenzyl bromide was added, and the mixture was reacted at roomtemperature for 20 hours. To the reaction mixture at 0° C. was added asaturated aqueous solution of ammonium chloride followed by extractionwith ethyl acetate. The organic layer was washed with water and thenconcentrated under reduced pressure. The residue thus obtained wassubjected to silica gel column chromatography for separation andpurification. Elution with dichloromethane yielded 1.57 g (3.93 mmol) of1,6-bis(4-bromophenyl)-2,5-dioxahexane.

To a solution of 1.57 g (3.93 mmol) of the above-obtained compound indry tetrahydrofuran (40 ml) at -78° C. was added 1.60M hexane solutionof n-butyllithium (6.20 ml, 9.92 mmol) in the atmosphere of argon, andthe mixture was allowed to react for 30 min. To the solution was added3.00 ml (40.9 mmol) of acetone, and the mixture was reacted at -78° C.for 10 min. followed by addition of a saturated aqueous solution ofammonium chloride and extraction with ethyl acetate. The organic layerwas washed with water and then concentrated under reduced pressure. Theresidue thus obtained was subjected to silica gel column chromatographyfor separation and purification. Elution with dichloromethane-methanol(25:1) yielded 1.07 g (3.28 mmol) of1,6-bis[4-(α-hydroxyisopropyl)phenyl]-2,5-dioxahexane.

To 1.07 g (3.28 mmol) of the above-obtained hydroxy compound were added10 ml of ether, 20 ml of a 30% aqueous solution of hydrogen peroxide and0.50 ml of concentrated sulfuric acid. The mixture was allowed to reactat room temperature for 17 hours followed by addition of water andextraction with ethyl acetate. The organic layer was washed with waterand then concentrated under reduced pressure. The residue thus obtainedwas subjected to silica gel column chromatography for separation andpurification. Elution with ethyl acetate-hexane (1:1) yielded 1.12 g(3.13 mmol) of 1,6-bis[4-(α-hydroxyisopropyl)phenyl]-2,5-dioxahexane.

NMR(ppm, CDCl₃)

8.10(s, 2 H), 7.52-7.14(m, 8 H), 4.53(s, 4 H),

3.62(s, 4 H), 1.55(s, 12 H).

IR(νcm⁻¹, CHCl₃) 3520, 3330.

EXAMPLE 30

Bis[2-chloro-4-(α-hydroperoxyisopropyl)benzyl]ether ##STR56##

To a solution of 271 mg (6.78 mmol) of sodium hydride contained at 60%in mineral oil in dry dimethylformamide (25 ml) was added 1.00 g (4.52mmol) of 4-bromo-2-chlorobenzyl alcohol in an atmosphere of argon, andthe mixture was allowed to react at 40°-50° C. for 30 min. Then, 1.54 g(5.42 mmol) of 4-bromo-2-chlorobenzyl bromide was added, and the mixturewas reacted at room temperature for 18 hours. To the reaction mixture at0° C. was added a saturated aqueous solution of ammonium chloridefollowed by extraction with ethyl acetate. The organic layer was washedwith water and then concentrated under reduced pressure. The residuethus obtained was subjected to silica gel column chromatography forseparation and purification. Elution with ethyl acetate-hexane (1:4)yielded 1.69 g (3.97 mmol) of bis(4-bromo-2-chlorobenzyl) ether.

To a solution of 1.69 g (3.97 mmol) of the above-obtained compound indry tetrahydrofuran (50 ml) at -78° C. was added a 1.60M hexane solutionof n-butyllithium (5.46 ml, 8.73 mmol) in the atmosphere of argon, andthe mixture was allowed to react for 30 min. To the solution was added4.00 ml (54.5 mmol) of acetone, and the mixture was reacted at -78° C.for 10 min. followed by addition of a saturated aqueous solution ofammonium chloride and extraction with ethyl acetate. The organic layerwas washed with water and then concentrated under reduced pressure. Theresidue thus obtained was subjected to silica gel column chromatographyfor separation and purification. Elution with dichloromethane-methanol(100:1) yielded 1.19 g (3.11 mmol) ofbis[2-chloro-4-(α-hydroxyisopropyl)benzyl] ether.

To 1.19 g (3.11 mmol) of the above-obtained hydroxy compound were added10 ml of ether, 30 ml of a 50% aqueous solution of hydrogen peroxide and0.2 ml of concentrated sulfuric acid. The mixture was allowed to reactat room temperature for 16 hours followed by addition of water andextraction with ethyl acetate. The organic layer was washed with waterand then concentrated under reduced pressure. The residue thus obtainedwas subjected to silica gel column chromatography for separation andpurification. Elution with ethyl acetate-hexane (2:1) yielded 947 mg(2.28 mmol) of bis[2-chloro-4-(α-hydroperoxyisopropyl)benzyl] ether.

NMR (ppm, CDCl₃)

8.03(s, 2 H), 7.47-7.14(m, 6 H), 4.69(s, 4 H),

1.55(s, 12 H)

IR(νcm⁻¹, CHCl₃) 3520, 3330

EXAMPLE 31

1,9-Bis[2-chloro-4-(α-hydroperoxyisopropyl)phenyl]-2,5,8-trioxanonane##STR57##

To a solution of 472 mg (11.8 mmol) of sodium hydride contained at 60%in mineral oil in dry dimethylformamide (50 ml) was added 500 mg (4.71mmol) of diethylene glycol in an atmosphere of argon, and the mixturewas allowed to react at 40°-50° C. for 30 min. Then, 2.96 g (10.4 mmol)of 4-bromo-2-chlorobenzyl bromide was added, and the mixture was reactedat room temperature for 16 hours. To the reaction solution at 0° C. wasadded a saturated aqueous solution of ammonium chloride followed byextraction with ethyl acetate. The organic layer was washed with waterand then concentrated under reduced pressure. The residue thus obtainedwas subjected to silica gel column chromatography for separation andpurification. Elution with ethyl acetatehexane (1:3) yielded 2.10 g(4.09 mmol) of 1,9-bis(4-bromo-2-chlorophenyl)-2,5,8-trioxanonane.

To a solution of 2.10 g (4.09 mmol) of the above-obtained compound indry tetrahydrofuran (40 ml) at -78° C. was added a 1.60M hexane solutionof n-butyllithium (5.63 ml, 9,00 mmol) in the atmosphere of argon, andthe mixture was allowed to react for 30 min. To the solution was added3.00 ml (40.9 mmol) of acetone, and the mixture was reacted at -78° C.for 10 min. followed by addition of a saturated aqueous solution ofammonium chloride and extraction with ethyl acetate. The organic layerwas washed with water and then concentrated under reduced pressure. Theresidue thus obtained was subjected to silica gel column chromatographyfor separation and purification. Elution with dichloromethane-methanol(50:1) yielded 1.44 g (3.06 mmol) of1,9-bis[2-chloro-4-(α-hydroxyisopropyl)phenyl]-2,5,8-trioxanonane.

To 1.44 g (3.06 mmol) of the above-obtained hydroxy compound were added10 ml of ether, 30 ml of a 50% aqueous solution of hydrogen peroxide and0.2 ml of concentrated sulfuric acid. The mixture was allowed to reactat room temperature for 18 hours followed by addition of water andextraction with ethyl acetate. The organic layer was washed with waterand then concentrated under reduced pressure. The residue thus obtainedwas subjected to silica gel column chromatography for separation andpurification. Elution with ethyl acetate-hexane (2:1) yielded 1.09 g(2.17 mmol) of1,9-bis[2-chloro-4-(α-hydroperoxyisopropyl)phenyl]-2,5,8-trioxanonane.

NMR (ppm, CDCl₃)

7.98(s, 2 H), 7.45-7.16(m, 6 H), 4.64(s, 4 H),

3.62(s, 8 H), 1.53(s, 12 H).

IR(νcm⁻¹, CHCl₃) 3530, 3330.

EXAMPLE 32

1,21-Bis[4-(α-hydroperoxyisopropyl)-2-methylphenyl]-2,5,8,11,14,17,20-heptaoxaheneicosane##STR58##

To a solution of 354 mg (3.85 mmol) of sodium hydride contained at 60%in mineral oil in dry dimethylformamide (20 ml) was added 1.00 g (3.54mmol) of hexaethylene glycol, and the mixture was reacted at 40°-50° C.for 30 min. Then, 2.06 g (7.79 mmol) of 4-bromo-2-methylbenzyl bromidewas added, and the mixture was allowed to react at room temperature for17 hours. To the reaction solution at 0° C. was added a saturatedaqueous solution of ammonium chloride followed by extraction with ethylacetate. The organic layer was washed with water and concentrated underreduced pressure. The residue thus obtained was subjected to silica gelcolumn chromatography for separation and purification. Elution withethyl acetate-hexane (1:4) yielded 2.02 g (3.12 mmol) of1,21-bis(4-bromo-2-methylphenyl)-2,5,8,11,14,17,20-heptaoxaheneicosane.

To a solution of 2.02 g (3.12 mmol) of the above-obtained compound indry tetrahydrofuran (30 ml) at -78° C. was added a 1.60M hexane solutionof n-butyllithium (4.29 ml, 6.86 mmol) in the atmosphere of argon, andthe mixture was allowed to react for 30 min. To the solution was added3.00 ml (40.9 mmol) of acetone, and the mixture was reacted at -78° C.for 10 min. followed by addition of a saturated aqueous solution ofammonium chloride and extraction with ethyl acetate. The organic layerwas washed with water and then concentrated under reduced pressure. Theresidue thus obtained was subjected to silica gel column chromatographyfor separation and purification. Elution with dichloromethane-methanol(100:1) yielded 1.37 g (2.25 mmol) of1,21-bis[4-(α-hydroxyisopropyl)-2-methylphenyl]-2,5,8,11,14,17,20heptaoxaheneicosane.

To 1.37 g (2.25 mmol) of the above-obtained hydroxy compound were added10 ml of ether, 30 ml of a 50% aqueous solution of hydrogen peroxide and0.2 ml of concentrated sulfuric acid. The mixture was allowed to reactat room temperature for 18 hours followed by addition of water andextraction with ethyl acetate. The organic layer was washed with waterand then concentrated under reduce pressure. The residue thus obtainedwas subjected to silica gel column chromatography for separation andpurification. Elution with ethyl acetate-hexane (2:1) yielded 1.07 g(1.67 mmol) of1,21-bis[4-(α-hydroperoxyisopropyl)-2-methylphenyl]-2,5,8,11,14,17,20-heptaoxaheneicosane.

NMR (ppm, CDCl₃)

8.07(s, 2 H), 7.42-7.03(m, 6 H), 4.53(s, 4 H),

3 61(s, 24 H), 2.24(s, 6 H), 1.56(s, 12 H).

IR(νcm⁻¹, CHCl₃) 3530, 3340.

EXAMPLE 33

N,N Bis[4-(α-hydroperoxyisopropyl)benzenesulfonyl]-piperazine ##STR59##

To a solution of 0.79 g (9.16 mmol) of piperazine in dry pyridine (20ml) was added 5.15 g (20.15 mmol) of 4-bromobenzenesulfonyl chloride inan atmosphere of argon, and the mixture was allowed to react at 0° C.for 3 hours. To the solution was added water followed by extraction withethyl acetate. The organic layer was washed with water and thenconcentrated under reduced pressure. The residue thus obtained wassubjected to silica gel column chromatography for separation andpurification. Elution with dichloromethane yielded 4.37 g (8.34 mmol) ofN,N'-bis(4-bromobenzenesulfonyl)piperazine.

To a solution of 4.37 g (8.34 mmol) of the above-obtained compound indry tetrahydrofuran (20 ml) at -78° C. was added a 1.60M hexane solutionof n-butyllithium (11.5 ml, 18.35 mmol) in the atmosphere of argon, andthe mixture was allowed to react for 30 min. To the solution was added10.0 ml (136 mmol) of acetone, and the mixture was reacted at -78° C.for 10 min. followed by addition of a saturated aqueous solution ofammonium chloride and extraction with ethyl acetate. The organic layerwas washed with water and then concentrated under reduced pressure. Theresidue thus obtained was subjected to silica gel column chromatographyfor separation and purification. Elution with dichloromethane-methanolyielded 2.72 g (6.42 mmol) ofN,N'-bis[4-(α-hydroxyisopropyl)benzenesulfonyl]piperazine.

To 2.72 g (6.42 mmol) of the above-obtained hydroxy compound were added15 ml of ether, 20 ml of a 30% aqueous solution of hydrogen peroxide and0.50 ml of concentrated sulfuric acid. The mixture was allowed to reactat room temperature for 17 hours followed by addition of water andextraction with ethyl acetate. The organic layer was washed with waterand then concentrated under reduced pressure. The residue thus obtainedwas subjected to silica gel column chromatography for separation andpurification. Elution with ethyl acetate-hexane (2:1) yielded 2.22 g(4.87 mmol) ofN,N'-bis[4-(α-hydroperoxyisopropyl)benzenesulfonyl]-piperazine.

NMR (ppm, CDCl₃)

7.83(s, 2 H), 7.67-7.16(m, 8 H), 2.82(s, 8 H),

1.61(s, 12 H).

IR(νcm⁻¹, CHCl₃) 3530, 3330.

EXAMPLE 34

1,3-Bis[4-(α-hydroperoxyisopropyl)benzyl]sulfone ##STR60##

To a solution of 1.85 g (9.11 mmol) of 4-bromobenzylmercaptan in drydichloromethane (30 ml) were added 2.72 g (10.9 mmol) of 4-bromobenzylbromide and 2.31 g (22.8 mmol) of triethylamine in an atmosphere ofargon, and the mixture was allowed to react at room temperature for 16hours. To the solution was added water followed by extraction with ethylacetate. The organic layer was washed with water and then concentratedunder reduced pressure. The residue thus obtained was subjected tosilica gel column chromatography for separation and purification.Elution with ethyl acetate-hexane (1:4) yielded 3.08 g (8.29 mmol) ofbis(4-bromobenzyl)sulfide.

To a solution of 3.08 g (8.29 mmol) of said compound in drytetrahydrofuran (50 ml) at -78° C. was added a 1.60M hexane solution ofn-butyllithium (11.4 ml, 18.2 mmol), and the mixture was allowed toreact for 30 min. To the solution was added 4.0 ml (54.5 mmol) ofacetone, and the mixture was allowed to react at -78° C. for 10 min.followed by addition of a saturated aqueous solution of ammoniumchloride and extraction with ethyl acetate. The organic layer was washedwith water and then concentrated under reduced pressure. The residuethus obtained was subjected to silica gel column chromatography forseparation and purification. Elution with dichloromethane-methanol(100:1) yielded 1.97 g (5.97 mmol) ofbis[4-(α-hydroxyisopropyl)benzyl]sulfide.

To 1.97 g (5.97 mmol) of the above-obtained hydroxy compound were added10 ml of ether, 20 ml of a 30% aqueous solution of hydrogen peroxide and0.50 ml of concentrated sulfuric acid. The mixture was allowed to reactat room temperature for 20 hours followed by addition of water andextraction with ethyl acetate. The organic layer was washed with waterand then concentrated under reduced pressure. The residue thus obtainedwas subjected to silica gel column chromatography for separation andpurification. Elution with ethyl acetate-hexane (3:1) yielded 1.58 g(4.36 mmol) of bis[4-(α-hydroperoxyisopropyl)benzyl]sulfone.

NMR (ppm, DMSO-d₆)

7.49(s, 8 H), 4.62(s, 4 H), 1.49(s, 12 H).

IR (νcm⁻¹, KBr) 3400.

EXAMPLE 35

2-[2-[α-[4-(α-hydroperoxyisopropyl)toluene]sulfonyl]-ethanesulfonyl]ethanesulfonylmethyl-4-(α-hydroperoxyisopropyl)benzene##STR61##

To a solution of 5.00 g (20.0 mmol) of 4-bromobenzyl bromide in drytetrahydrofuran (24 ml) was added 1.30 ml (9.97 mmol) of 2-marcaptoethylsulfide in an atmosphere of argon, and the mixture was allowed to reactat 0° C. for 6 hours. To the solution was added water followed byextraction with benzene. The organic layer was washed with water andthen concentrated under reduced pressure. The residue thus obtained wassubjected to silica gel column chromatography for separation andpurification. Elution with dichloromethane-hexane (1:5) yielded 4.46 g(9.69 mmol) of 1,9-bis(4-bromobenzene)-2,5,8-trithianonane.

To a solution of 4.46 g (9.68 mmol) of the above-obtained compound in 30ml of dry tetrahydrofuran at -78° C. was added a 1.60M hexane solutionof n-butyllithium (18.8 ml, 30.0 mmol) in the atmosphere of argon, andthe mixture was allowed to react for 30 min. To the solution was added10.0 ml (136 mmol) of acetone, and the mixture was allowed to react at-78° C. for 10 min. followed by addition of a saturated aqueous solutionof ammonium chloride and extraction with ethyl acetate. The organiclayer was washed with water and then concentrated under reducedpressure. The residue thus obtained was subjected to silica gel columnchromatography. Elution with dichloromethane yielded 3.36 g (7.45 mmol)of 1,9-bis[4-(α-hydroxyisopropyl)phenyl]-2,5,8-trithianonane.

To 3.36 g (7.45 mmol) of the above-obtained hydroxy compound were added20 ml of ether, 20 ml of a 30% aqueous solution of hydrogen peroxide and0.50 ml of concentrated sulfuric acid. The mixture was allowed to reactat room temperature for 19 hours followed by addition of water andextraction with ethyl acetate. The organic layer was washed with waterand then concentrated under reduced pressure. There was obtained 3.15 g(5.44 mmol) of2-[2-[α-[4-(α-hydroperoxyisopropyl)toluene]sulfonyl]ethanesulfonyl]-ethanesulfonylmethyl-4-(α-hydroperoxyisopropyl)benzene.

NMR (ppm, DMSO-d₆)

7.38(s, 8 H), 4.57(s, 4 H), 3.62(s, 8 H), 1.45(s,

12 H).

IR (νcm⁻¹, KBr) 3400.

EXAMPLE 36

N,N'-Bis[4-(α-hydroperoxyisopropyl)benzenesulfonyl]-N,N'-dimethyl-3,6,9-trioxaundecane-11-diamine##STR62##

To a solution of 1.64 g (8.44 mmol) of tetraethylene glycol in drypyridine (30 ml) was added 3.55 g (18.6 mmol) of p-toluenesulfonylchloride in an atmosphere of argon, and the mixture was allowed to reactat room temperature for 15 hours. To the solution was added waterfollowed by addition of conc. hydrochloric acid to adjust the pH to 4,and the resulting mixture was extracted with ethyl acetate. The organiclayer was washed with water and then concentrated under reducedpressure. The residue thus obtained was subjected to silica gel columnchromatography for separation and purification. Elution withdichloromethane-methanol (100:1) yielded 3.78 g (7.52 mmol) ofO,O'-ditosyl-3,6,9-trioxaundecane-1,11-diol.

To a solution of 9.38 g (36.7 mmol) of p-toluenesulfonyl chloride in drypyridine was added 12.4 g (184 mmol) of methylamine hydrochloride in theatmosphere of argon, and the mixture was allowed to react at roomtemperature for 4 hours. To the solution was added water followed byextraction with ethyl acetate. The organic layer was washed with waterand then concentrated under reduced pressure. The residue thus obtainedwas subjected to silica gel column chromatography for separation andpurification. Elution with dichloromethane yielded 8.46 g (33.8 mmol) of4-bromobenzenesulfonyl N-methylamide.

To a solution of 1.56 g (39.1 mmol) of sodium hydride contained at 60%in mineral oil in dry dimethylformamide (50 ml) was added 4.70 g (18.8mmol) of 4-bromobenzenesulfonyl-N-methylamide in the atmosphere ofargon, and the mixture was allowed to react at room temperature for 30min. Then, 3.78 g (7.52 mmol) ofO,O'-tosyl-3,6,9-trioxaundecane-1,11-diol was added, and the mixture wasallowed to react for 18 hours. The solution was added to ice waterfollowed by extraction with ethyl acetate. The organic layer was washedwith water and then concentrated under reduced pressure. The residuethus obtained was subjected to silica gel column chromatography forseparation and purification. Elution with dichloromethane yielded 4.66 g(7.07 mmol) ofN,N'-(4-bromobenzenesulfonyl)-N,N'-dimethyl-3,6,9-trioxaundecane-1,11-diamine.

To a solution of 4.66 g (7.07 mmol) of the above-obtained compound indry tetrahydrofuran (50 ml) at -78° C. was added a 1.60M hexane solutionof n-butyllithium (9.8 ml, 15.6 mmol) in the atmosphere of argon, andthe mixture was allowed to react for 30 min. To the solution was added4.0 ml (54.5 mmol) of acetone, and the mixture was allowed to react at-78° C. for 10 min. followed by addition of a saturated aqueous solutionof ammonium chloride and extraction with ethyl acetate. The organiclayer was washed with water and then concentrated under reducedpressure. The residue thus obtained was subjected to silica gel columnchromatography for separation and purification. Elution with ethylacetatehexane (1:4) yielded 3.18 g (5.16 mmol) ofN,N'-[4-(α-hydroxyisopropyl)benzenesulfonyl]-N,N'-dimethyl-3,6,9-trioxaundecane-1,11-diamine.

To 3.18 g (5.16 mmol) of the above-obtained hydroxy compound were added10 ml of ether, 20 ml of a 30% aqueous solution of hydrogen peroxide and0.50 ml of concentrated sulfuric acid. The mixture was allowed to reactat room temperature for 17 hours followed by addition of water andextraction with ethyl acetate. The organic layer was washed with waterand then concentrated under reduced pressure. The residue thus obtainedwas subjected to silica gel column chromatography for separation andpurification. Elution with dichloromethane-methanol (50:1) yielded 2.54g (3.92 mmol) ofN,N'-[4-(α-hydroperoxyisopropyl)benezenesulfonyl]-N,N'-dimethyl-5,6,9-trioxaundecane-1,11-diamine.

NMR (ppm, CDCl₃)

7.82(s, 2 H), 7.60(s, 8 H), 3.57(t, 4H, J=5 Hz),

3.53(s, 8 H), 3.18(t, 4H, J=5 Hz), 2.81(s, 6 H),

1.62(s, 12 H).

IR (νcm⁻¹,CHCl₃) 3532, 3330.

EXAMPLE 37

N,N'-Bis[4-(α-hydroperoxyisopropyl)benzenesulfonyl]-N,N'-dimethyl-3,6,9,12,15-pentaoxaheptadecane-1,17-diamine##STR63##

To a solution of 1.48 g (5.24 mmol) of hexaethylene glycol in drypyridine (30 ml) was added 2.19 g (11.5 mmol) of p-toluenesulfonylchloride in an atmosphere of argon, and the mixture was allowed to reactat room temperature for 15 hours. To the solution was added waterfollowed by addition of conc. hydrochloric acid to adjust the pH to 4,and the resulting mixture was extracted with ethyl acetate. The organiclayer was washed with water and then concentrated under reducedpressure. The residue thus obtained was subjected to silica gel columnchromatography for separation and purification. Elution withdichloromethane-methanol (100:1) yielded 2.85 g (4.82 mmol) ofO,O'-ditosyl-3,6,9,12,15-pentaoxaheptadecane-1,17-diol.

To a solution of 3.14 g (12.3 mmol) of 4-bromobenzenesulfonyl chloridein dry pyridine was added 4.15 g (61.5 mmol) of methylaminehydrochloride in the atmosphere of argon, and the mixture was allowed toreact at room temperature for 4 hours. To the solution was added waterfollowed by extraction with ethyl acetate. The organic layer was washedwith water and then concentrated under reduced pressure. The residue wassubjected to silica gel column chromatography for separation andpurification. Elution with dichloromethane yielded 2.69 g (11.6 mmol) of4-bromobenzenesulfonyl-N-methylamide.

To a solution of 1.02 g (25.5 mmol) of sodium hydride contained at 60%in mineral oil in dry dimethylformamide (50 ml) was added 2.96 g (11.6mmol) of 4-bromobenzenesulfonyl-N-methylamide in the atmosphere ofargon, and the mixture was allowed to react at room temperature for 30min. Then, 2.85 g (4.82 mmol) of O,O'-ditosyl-3,6,9,12,15-pentaoxaheptadecane-1,17-diol, and the resulting mixture wasallowed to react for 22 hours. The solution was added to ice waterfollowed by extraction with ethyl acetate. The organic layer was washedwith water and then concentrated under reduced pressure. The residueobtained was subjected to silica gel column chromatography forseparation and purification. Elution with dichloromethane yielded 3.28 g(4.39 mmol) ofN,N'-bis(4-bromobenzenesulfonyl)-N,N'-dimethyl-3,6,9,12,15-pentaoxaheptadecane-1,17-diamine.

To a solution of 3.28 g (4.39 mmol) of the above-obtained compound indry tetrahydrofuran (50 ml) at -78° C. was added a 1.60M hexane solutionof n-butyllithium (6.0 ml, 9.66 mmol) in the atmosphere of argon, andthe mixture was allowed to react for 30 min. To the solution was added4.0 ml (54.5 mmol) of acetone, and the mixture was allowed to react at-78° C. for 10 min. followed by addition of a saturated aqueous solutionof ammonium chloride and extraction with ethyl acetate. The organiclayer was washed with water and then concentrated under reducedpressure. The residue thus obtained was subjected to silica gel columnchromatography for separation and purification. Elution with ethylacetatehexane (1:4) yielded 2.35 g (3.34 mmol) ofN,N'-bis[4-(α-hydroxyisopropyl)benzenesulfonyl]-N,N'-dimethyl-3,6,9,12,15-pentaoxaheptadecane-1,17-diamine.

To 2.35 g (3.34 mmol) of the above-obtained hydroxy compound were added10 ml of ether, 20 ml of a 30% aqueous solution of hydrogen peroxide and0.50 ml of concentrated sulfuric acid. The mixture was allowed to reactat room temperature for 17 hours followed by addition of water andextraction with ethyl acetate. The organic layer was washed with waterand then concentrated under reduced pressure. The residue thus obtainedwas subjected to silica gel column chromatography for separation andpurification. Elution with dichloromethane-methanol (50:1) yielded 1.89g (2.57 mmol) ofN,N'-bis[4-(α-hydroperoxyisopropyl)benzenesulfonyl]-N,N'-dimethyl-3,6,9,12,15-pentaoxaheptadecane-1,17diamine.

NMR (ppm, CDCl₃)

7.86(s, 2 H), 7.53(s, 8 H), 3.54(t, 4H, J=5 Hz),

3.52(s, 16 H), 3.09(t, 4H, J=5 Hz), 2.90(s, 6 H),

1.65(s, 12 H).

IR (νcm⁻¹, CHCl₃) 3530, 3340.

EXAMPLE 38

    ______________________________________                                        Preparative method of test paper                                              Solution I                                                                    ______________________________________                                        α-Hydroperoxyisopropylphenyl compound (I) or (II)                        ##STR64##                                                                    (m is number of the hydroperoxy group                                         contained in one molecule)                                                    p-Toluenesulfonyl-N-diethylamide                                                                         5.0    g                                           Sodium dioctylsulfosuccinate                                                                             1.5    g                                           Ethanol                    100    ml                                          ______________________________________                                    

A filter paper is thoroughly made wet with Solution I and dried in adrying oven at 40° C. for 20 min.

    ______________________________________                                        Solution II                                                                   ______________________________________                                        Acrylamide              10     g                                              Polyethylene glycol     10     g                                              Trisodium citrate dihydrate                                                                           9      g                                              Citric acid monohydrate 1      g                                              Saponin                 100    mg                                             EDTA-2Na                30     mg                                             Water                   100    ml                                             ______________________________________                                    

The filter paper treated with Solution I and dried is thoroughly madewet with Solution II and dried in a drying oven at 40° C. for 50 min.

    ______________________________________                                        Solution III                                                                  ______________________________________                                        Orthotolidine         1.20   g                                                3-Aminoquinoline      0.5    g                                                Benzene               100    ml                                               ______________________________________                                    

The filter paper treated with Solution II and dried is thoroughly madewet with Solution III and dried in a drying oven at 40° C. for 10 min.This is used as a test paper for evaluation.

TEST EXAMPLE 1

The test paper prepared as described in the preparative example issoaked in a specimen for one second. Referring to a selected color tonetable, color development of the above-mentioned test paper is read bynaked eyes in terms of the judgement code indicated in the color tonetable. On the basis of the degree of color development according to saidcolor tone table, concentration of the occult blood in the specimen isjudged. Correlations between the judgement code and the hemoglobinconcentration are shown below.

                  TABLE 1                                                         ______________________________________                                        Judgement code                                                                             Hemoglobin concentration                                         ______________________________________                                        3+           250/μl                                                        2+           50/μl                                                         +            10/μl                                                         ______________________________________                                    

It is noted that the color tone correlated to the hemoglobinconcentration in the color tone table indicates color of the test pieceprepared by the method described in the preparative example using aperoxide, 2,5-dimethylhexane-2,5-dihydroperoxide judged after 60seconds.

As a result, 4-(α-hydroperoxyisopropyl)benzyl benzyl ether and4-(2,4,7-trioxaoctyl)cumene hydroperoxide andbis[4-(α-hydroperoxyisopropyl)benzyl] ether developed the colorcorresponding to the color tone table judged after approximately 10seconds, whereasN,N-dimethyl-[4-(α-hydroperoxyisopropyl)benzene]sulfoamide afterapproximately 20 seconds. On the other hand, it required approximately25 seconds for the test paper with cumene hydroperoxide to develop thecolor corresponding to the color tone table. Note that it requires 60seconds for 2,5-dimethylhexane-2,5-dihydroperoxide used for thepreparation of the color tone table.

The above findings indicated that the α-hydroperoxyisopropylphenylcompound (I) or (II) is more highly sensitive than2,5-dimethylhexane-2,5-dihydroperoxide or cumene hydroperoxide, which isused in commercially available test papers for the measurement of occultblood in urine.

Next, results of the judgement in the test conducted after storage of 2weeks or 4 weeks at 60° C. are shown in Table 2.

                  TABLE 2                                                         ______________________________________                                        Hemoglobin concentration                                                      Storage condition                                                             60° C., 2 weeks                                                                             60° C., 4 weeks                                   Test    Time for judgement                                                    compound                                                                              30 seconds                                                                              60 seconds 30 seconds                                                                            60 seconds                               ______________________________________                                        A       +˜2+                                                                              2+         +       +˜2+                               B       2+        2+˜3+                                                                              +˜2+                                                                            2+                                       C       2+        2+˜3+                                                                              +˜2+                                                                            2+                                       D       +˜2+                                                                              2+         0˜+                                                                             +                                        E       0         0          0       0                                        F       +         +˜2+ 0       0                                        G       0˜+ +          0       0                                        ______________________________________                                         Note                                                                          The indications 0˜+, +˜2+ and 2+˜3+ indicate a color        tone ranged between the numbers indicated. The indication 0˜⊕       indicates a middle color tone nearer to +.                               

TEST COMPOUND

A: 4(2,4,7-Trioxaoctyl)cumene hydroperoxide

B: 4-(α-Hydroperoxyisopropyl)benzyl benzyl ether

C: Bis[4-(α-hydroperoxyisopropyl)benzyl]benzyl ether

D: N,N-Dimethyl-[4-(α-hydroperoxyisopropyl)benzene]-sulfoamide

E: Cumene hydroperoxide (Control)

F: 4-Octylcumene hydroperoxide (Control)

G: 2,5-Dimethylhexane-2,5-dihydroperoxide (Control)

It is seen from Table 2 that 4-(α-hydroperoxyisopropyl)benzyl benzylether, 4-(2,4,7-trioxaoctyl)cumene hydroperoxide,bis[4-(α-hydroperoxyisopropyl)benzyl]ether andN,N-dimethyl-]4-(α-hydroperoxyisopropyl)benzene]sulfoamide of theinvention are superior in stability with elapse of time. Particularly,comparison between 4-(2,4,7-trioxaoctyl)cumene hydroperoxide and4-octylcumene hydroperoxide reveals usefulness of the ether bond.

TEST EXAMPLE 2

There is contained vitamin C in human urine owing to drinking water,vitamin preparations, etc. Test paper for the measurement of occultblood in urine undergoes pseudonegative reaction due to the presence ofvitamin C. A performance test was carried out with theα-hydroperoxyisopropylphenyl compound (I) or (II) using the test pieceprepared by the method shown in the preparative example in the presenceof vitamin C at a concentration of 20 mg/dl or 100 mg/dl. Results areshown in Table 3 and Table 4.

                                      TABLE 3                                     __________________________________________________________________________    Vitamin C concentration in urine at 20 mg/dl                                  Hemoglobin concentration                                                      10/μl       50/μl       250/μl                                       +              2+             3+                                              Time for judgement (sec.)                                                     10    30  60 (sec.)                                                                          10   30   60 (sec.)                                                                          10 30  60 (sec.)                                __________________________________________________________________________    A 0˜⊕                                                                     0˜⊕                                                                     0    2+   2+   2+   3+ 3+< 3+<                                      B +   0˜⊕                                                                     0    2+˜3+                                                                        2+˜3+                                                                        2+˜3+                                                                        3+ 3+< 3+<                                      C +   0˜⊕                                                                     0    2+˜3+                                                                        2+˜3+                                                                        2+˜3+                                                                        3+ 3+< 3+<                                      E 0˜⊕                                                                     0˜+                                                                         0     +˜2+                                                                        2+   2+   3+ 3+< 3+<                                      F 0   0   0    +    +    +    2+ 2+  2+                                       G 0   0   0    +     + ˜2+                                                                       2+   2+ 3+  3+                                       __________________________________________________________________________

                                      TABLE 4                                     __________________________________________________________________________    Vitamin C concentration in urine at 100 mg/dl                                 Hemoglobin concentration                                                      10/μl   50/μl       250/μl                                           +          2+             3+                                                  Time for judgement (sec.)                                                     10  30                                                                              60 (sec.)                                                                          10   30   60 (sec.)                                                                          10 30 60 (sec.)                                     __________________________________________________________________________    A 0 0 0    +˜2+                                                                         +    0    3+ 3+ 3+                                            B 0 0 0    2+   +˜2+                                                                         0˜⊕                                                                      3+ 3+ 3+                                            C 0 0 0    2+   +˜2+                                                                         0˜⊕                                                                      3+ 3+ 3+                                            E 0 0 0    +˜2+                                                                         +    0    3+ 3+ 3+                                            F 0 0 0    +    0˜+                                                                          0    2+ 2+ 2+                                            G 0 0 0    0˜+                                                                          0˜+                                                                          0    2+ 3+ 2+˜3+                                   __________________________________________________________________________

It is seen from the results in Tables 3 and 4 that the peroxides of theinvention, 4-(α-hydroperoxyisopropyl)benzyl benzyl ether and4-(2,4,7-trioxaoctyl)cumene hydroperoxide andbis[4-(α-hydroperoxyisopropyl)benzyl]ether had a vitamin C-inhibitoryeffect equal to or more than that of cumene hydroperoxide, and also thatcomparison between 4-(2,4,7-trioxaoctyl)cumene hydroperoxide and4-octylcumene hydroperoxide reveals effectiveness of the side chaincontaining the ether bond.

TEST EXAMPLE 3

It is known that when the test piece for the measurement of occult bloodand the test piece for the measurement of glucose are adjacent eachother on a stick, discoloration is produced in the test paper for themeasurement of glucose.

Test pieces prepared according to the above preparative example using asthe peroxide 4-(α-hydroperoxyisopropyl)benzyl benzyl ether,4-(2,4,7-trioxaoctyl)cumene hydroperoxide,bis[4-(α-hydroperoxyisopropyl)benzyl] ether andN,N-dimethyl-[4-(α-hydroperoxyisopropyl)benzenesulfoamide, and a testpiece using 2,5-dimethylhexane-2,5-dihydroperoxide respectively wereplaced on a separate stick. A test piece for glucose was placed at theadjacent site on each of the sticks which were stored at 40° C. for onemonth. Whereas the former did not produce discoloration on the glucosetest piece, the latter produced discoloration. This indicates that theperoxides of the invention produce little influence upon the otheradjacent test item.

Industrial Applicability

The α-hydroperoxyisopropylphenyl compounds (I) or (II) are effectivelyused for detecting peroxide-active substances, particularly blood orhemoglobin. As a matter of fact, when the α-hydroperoxyisopropylphenylcompound (I) or (II) of the invention is used as an organichydroperoxide in peroxide-active substance-testing compositions or testdevices consisting of an organic hydroperoxide and a color-developingindicator, there are provided test compositions and test devices havingthe following characteristics:

(1) Being stable with elapse of time and capable of maintaining goodsensitivity even if stored for a long period of time.

(2) In case of multi-item test pieces for detecting components of urine,producing no discoloration on other adjacent test pieces such as thatfor glucose with no reduction of the performance associated.

(3) Being faster in the color-developing reaction and higher in thesensitivity for color development than prior-art test compositions.

Therefore, the present invention is utilized in a field of medicalinstrument industry.

What is claimed is:
 1. An α-hydroxyperoxyisopropylphenyl compound havingthe general formula ##STR65## wherein X represents a straight- orbranched-chain alkylene group which may contain an ether bond in thechain or a divalent organic group containing sulfur atom and R⁴ and R⁵are the same or different and respectively represent hydrogen atom, alower alkyl group, a halogen atom, carboxyl group or nitro group.
 2. Acompound of the general formula according to claim 1, wherein thealkylene group in X is a group having 2-100 carbon atoms.
 3. A compoundof the general formula according to claim 1 wherein the alkylene groupin X is an alkylene group represented by the formula given below.##STR66##
 4. A process for preparing α-hydroperoxyisopropylphenylcompounds having the general formula according to claim 1 whichcomprises oxidizing with an aqueous solution of hydrogen peroxide ofα-hydroxyisopropylphenyl compound having the general formula ##STR67##wherein R⁴ -R⁵ and X respectively have the same meanings as defined inclaim
 1. 5. A test composition for the measurement of peroxide-activesubstances comprising an α-hydroperoxyisopropylphenyl compound havingthe general formula according to claim 1 and an oxidation colorationindicator.
 6. A composition according to claim 5 wherein the oxidationcoloration indicator is orthotolidine, benzidine or leucomalachitegreen.
 7. A test device for the measurement of peroxide-activesubstances comprising a carrier on which a composition containing anα-hydroperoxyisopropylphenyl compound having the general formulaaccording to claim 1 and an oxidation coloration indicator is carried.8. A test device according to claim 7 wherein the carrier is non-wovencloth made of filter paper, glass fibers or a plastic material.
 9. Acompound of the formula according to item 1 wherein the organic groupsR⁴ and R⁵ are hydrogen or a lower alkyl, and the alkylene group in X isa group having 2-100 carbon atoms and containing an ether bond.